Coating composition comprised of a hydrophilic crosslinker, a hydrophobic crosslinker and optionally a hydrogel and methods of making and using the same

ABSTRACT

The present invention relates to coatings for devices such as medical devices that are useful for coating a variety of different types of material surfaces, including polymer and metal surfaces. The present invention also includes the method of using the coated device and methods to make the coated device and coating.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/490,752, filed Sep. 3, 2019, which is a national stage applicationunder 35 U.S.C. § 371 and claims the benefit of PCT Application No.PCT/US2018/020924 having an international filing date of Mar. 5, 2018,which designated the United States, which PCT application claimed thebenefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional PatentApplication Ser. No. 62/466,541, filed on Mar. 3, 2017. The entiredisclosures of U.S. patent application Ser. No. 16/490,752, PCTApplication No. PCT/US2018/020924 and U.S. Provisional PatentApplication No. 62/466,541 are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to coatings for devices, the method ofmaking the coating, the method of coating a device, and the method ofusing a device with a coating.

BACKGROUND

Many coatings for polymers and metals are described in the literature.Most are specific for a metal or a polymer, but not both. When more thanone material is used for a device, separate solutions are required tobond coatings to the different materials. Similarly, multiple solutionscan be needed if more than one polymer is used in a device as thedifferent polymers, similar to other materials like metal, can havediffering hydrophilicity. Many require surface activation in order tobond the coating to the surface of a substrate. Furthermore, knowncoating processes require multiple coating processes to coat a device.

SUMMARY

An aspect of the present invention is directed to a coating compositionthat includes hydrophobic/hydrophilic or polar gradient in a coatingsuch that the coating includes a hydrophilic crosslinker (as compared tothe hydrophobic carrier in the coating) and a hydrophobic crosslinker,which are at least partially miscible. In some embodiments, the coatingcan also include a polymer or hydrogel. Other aspects of the inventioninclude methods of making the coating, methods of using the coating, anddevices containing the coating.

The hydrophilic and hydrophobic crosslinkers or chain extendingmolecules are reactive molecules that can adhere to surfaces andcrosslink and extend high molecular weight polymer coatings.Advantageously, the coating can be used on different surfaces. At leastone crosslinking material can be, for example a triacrylate or othersimilar molecules, compounds containing these molecules, andcombinations thereof. The crosslinking materials can be used to obtain adifferential distribution of the crosslinker in the coating. Otherexamples of crosslinking materials can include vinyl siloxane, vinylpyrrolidone, methacrylic acid, hydroxyethyl methacrylate, a diacrylate,a di- or tri vinyl functional compound, a methyl-propyl, benzylcompounds with vinyl functional groups, and combinations thereof. Thesehydrophilic and hydrophobic reactive molecules can be miscible to someextent, acting as cross-linkers and chain extenders for polymericcoatings. The crosslinked polymer can entrap a polymer. The polymer canbe a hydrogel. The polymer can be polyvinylpyrrolidone (PVP). Otherpolymers can include a polyvinyl alcohol, a polyacrylate, an agarose, amethylcellulose, hyaluronic acid, polyisocyanates, a urethane coating, awater miscible epoxide, an alginate, or combinations of two or more ofthese polymers. The crosslinkers can be induced to crosslink and formthe crosslinked polymer by free radical, ionic or other mechanisms.

The composition of the surface to be coated with the composition of thepresent invention, for example, a medical device, can determine which ofthe cross-linkers (i.e., hydrophilic or hydrophobic crosslinkers) willbe preferentially adsorbed to the surface. This surface composition canmake the first reaction between the surface and the adsorbed crosslinkerpreferential or proceed at a more efficient or higher rate than theother crosslinker(s). When a second crosslinker is used in the coating,the second crosslinker can align in the coating according to thepolarity or hydrophobic/hydrophilic characteristics. Combinations ofdifferent cross-linkers and the substrate can be adjusted to optimizethe bonding, thickness or lubricity of the final product.

In some embodiments, the coating can have a variable concentration ofcomponents that are hydrophilic nature, which can be determined by thethickness of the coating or the concentration of the coating solution.The thickness of the coating can be controlled by the crosslinkingcomponents, which can be acrylates in some embodiments. The thicknesscan also be controlled by the extraction rate of the coating solution tothe substrate.

The crosslinking component can entrap the polymer, for example PVP. Thestratification of crosslinking components in the coating can result in avariable hydrophilic nature of the coating, can provide higher strengthof the coating near the substrate, and control the hydrogel waterabsorption near the surface.

The present invention has advantages over the prior art and addressesthe need for separate solutions to bond to metals and polymers ofdiffering polarity, hydrophilicity and hydrophobicity. The use ofcoatings that contains gradients of hydrophobic and hydrophiliccrosslinkers/compounds allows for a single coating process, regardlessof the material of the substrate to be coated. Advantageously, the useof these different compounds also allows for multiple compounds to bebonded or attached to the coating.

An aspect of the invention is a coated substrate. The coated substrateincludes a substrate that has a polar characteristic at an exteriorsurface. The coated substrate also has a gradient coating which includesat least one crosslinker. The coating has a variable concentration ofthe crosslinker between an substrate surface and an outer surface of thegradient coating. The substrate surface of the gradient coating isadjacent to the exterior surface of the substrate. The substrate surfaceof the gradient coating has a first coating polar characteristic and theouter surface of the gradient coating comprises a second coating polarcharacteristic.

An aspect of the invention is a method to coat a substrate. The methodincludes mixing at least one crosslinker, at least one polymer, and aninitiator to produce a pre-coating mixture. The mixture is applied tothe substrate. A reaction of the crosslinker is initiated to produce thea gradient crosslinked coating on the substrate. The crosslinked coatingentraps the polymer. The coating has a variable concentration of thecrosslinker between an substrate surface of the coating and an outersurface of the coating. The substrate surface of the coating is adjacentto the exterior surface of the substrate. The substrate surface of thecoating comprises a first coating polar characteristic and the outersurface of the coating comprises a second coating polar characteristic.

An aspect of the invention is a gradient coating. The coating includesat least one crosslinker, and a high molecular weight polymer.

An aspect of the invention is a method to produce a pre-coating. Themethod includes mixing at least one crosslinker, a high molecular weightpolymer, and an initiator to produce a pre-coating. A ratio of thecrosslinker, the high molecular weight polymer and the initiator isbetween about 1:0.1:0.005 and about 0.02:1.0:0.02.

An aspect of the invention is a pre-coating material for use on amedical device. The material includes a crosslinker, an initiator, and ahigh molecular weight polymer. The ratio of the crosslinker, the highmolecular weight polymer, and the initiator is between about 1:0.1:0.005and about 0.02:1.0:0.02.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 illustrates an embodiment of the present invention utilizing twocrosslinkers or network former to form the crosslinked polymer, and ahigh molecular weight polymer.

DETAILED DESCRIPTION

An aspect of the invention is a coated substrate. The substrate includesa polar characteristic on its exterior surface. The coating includes atleast one crosslinker. The crosslinker includes a variable concentrationbetween an substrate surface of the coating and an outer surface of thecoating. The substrate surface of the coating has a first coating polarcharacteristic and the outer surface of the coating has a second coatingpolar characteristic. The substrate surface of the coating is adjacentor in contact with the surface of the exterior surface of the substrate.

The substrate can be contact lenses, catheters (including cardiovascularcatheters and urological catheters), wires (including guidewires),springs, leads (for example a pacemaker lead), stents, implants,antennas, sensors, tubing, syringes, catheters, i.v. bag needles,needles, ventricular assist device components, and trochars, orcombinations of two or more of these devices. The material of thesubstrate can be a polymer, a metal, a glass, polyester block amides(for example Pebax™, a silicone rubber, nylons, polyvinylchlorides,styrene ethylene butadienes (SEBs), and combinations thereof. In someembodiments, the polar characteristic of the exterior surface of thesubstrate can be altered to assist in bonding of the coating, or toalter the stratification of the components based on the componentspolarity or hydrophobic/hydrophilic nature at the surface between thecoating and the substrate or on the exterior or outer surface of thecoating. By way of example, the polar characteristic of the exteriorsurface of a substrate can be altered from hydrophobic to lesshydrophobic as compared to its initial polar characteristic, or fromhydrophilic to less hydrophilic as compared to its initial polarcharacteristic. When more than one material is used in a medical device,the polar characteristic of the substrate can be different at differentlocations corresponding to the different materials. The medical devicecan be used in contact with blood, plasma, and the like.

The polar characteristic of the substrate can result in the substratebeing hydrophobic or hydrophilic. The polar characteristic can varythrough the coating, such that the coating is hydrophobic at ansubstrate surface of the coating, gradually increasing in hydrophilicproperties to the exterior surface which is more hydrophilic, or atleast less hydrophobic, compared to the characteristic at the substratesurface of the coating. Alternatively, the polar characteristic can varythrough the coating, such that the coating is hydrophilic at ansubstrate surface of the coating, then gradually decreases inhydrophilic properties, such that the exterior surface is hydrophobic,or at least less hydrophilic, compared to the characteristic at thesubstrate surface of the coating. If more than one crosslinking materialis utilized, the additional crosslinker can also vary in a similarmanner as the first crosslinking material. For example, if a firstcrosslinker is more hydrophilic than a second crosslinker, and asubstrate is hydrophilic, the crosslinking components can align suchthat the first crosslinker is adjacent to the surface of the substrateand second crosslinker in the coating is closer to the outer surface ofthe coating. If additional crosslinkers are used in the coating, thevariation and alignment of the additional crosslinkers can be located inthe coating based on the polarity and hydrophobic/hydrophilic naturecompared to other crosslinking materials in the coating. In someembodiments when more than one crosslinker is utilized, the differentcrosslinkers can not only crosslink with other similar crosslinkers, butcan also crosslink with different crosslinkers, which can result inadditional polarities of the crosslinked material within the overallcrosslinked material. The variation can be a result of variableconcentrations of the crosslinker in the coating. FIG. 1 illustrates anembodiment of the present invention utilizing two crosslinkers and PVPas the polymer.

The term crosslinker is used throughout the description of the inventionto include both monomers that crosslink to form a crosslinked polymerand network formers, which are long chain compounds that can intertwinewith itself, for example methacrylic acid.

In some embodiments, for example where only one crosslinker is utilizedin the coating, layering of the coating can be achieved based on thedensity variations in the coatings. In some embodiments, the coating canbe more dense at an substrate surface where the coating bonds orassociates to a surface of the substrate and less dense on the exteriorsurface of the coating. In other embodiments, the coating can be lessdense at an substrate surface compared to the density of the coating atan outer surface.

The polar characteristic of the coating can allow for the coating andthe substrate to create a bond. Thus, an advantage of the presentinvention is that the coating adheres to the substrate. The strength ofthe bond between the substrate and the coating can be between about 1 gmand about 500 gm. In some embodiments, when the entire substrateincludes the coating, then the coating can bond to itself forming asleeve around the substrate. The sleeve embodiment can be useful wherethe substrate is not likely to bond to the coating, but can also provideadditional strength between the coating and the substrate even when thecoating and the substrate create a bond.

The coating can be tailored for particular applications. For example, ifan application requires that the bond between the substrate and thecoating is strong, then the coating can be tailored so that it bondswith the substrate. For example, if the substrate is a polymer and theexterior surface of the polymer substrate is hydrophobic, then thecoating can be formed such that the coating exhibits a gradient wherethe hydrophobic crosslinker is close to the substrate and morehydrophilic crosslinkers are located at the surface. Embodiments of theinvention can result in the middle of the film providing additionalstrength to the coating by mono-functional network formers that haveintermediate concentration of the crosslinker that is designed to adsorbto the surface of the substrate and that of the crosslinker or networkformer selected to reside on the film surface. The vinyl polyethyleneand polypropylene oxides are such compounds which can be used as acrosslinker. Other embodiments can increase the water content of thecoating by addition of hydroxylated compounds as methacrylic acid (MAA),which can be used as a crosslinker. More than one of these embodimentscan be combined to tailor the coating for a particular application.Furthermore, it is possible to produce more than one layer or more thanone coating layers such that there are multiple layers in the coatingcreated by using the same or different coating materials on thesubstrate. In some embodiments, the coating can comprise between aboutone and about five layers, where each layer can be the same ordifferent. The coating can be on a portion of the first surface of thesubstrate such that between about 1% and about 99% of the first surfaceis coated with the coating. The coating can be on a portion of one ormore surfaces of the substrate such that between about 1% and about 99%of at least one surface of the substrate can be coated. In someembodiments, the coating can be on the entire first surface or on morethan one surface of the substrate such that it covers each surface ofthe substrate.

The gradient can be modulated by the choice of solvent used with thecoating, the drying time (evaporation rate), temperature, and itspolarity. By decreasing the polarity with a less polar solvent, a lesspolar crosslinker or network former can disperse into the coating. Amore polar solvent can force a less polar crosslinker to the surface ofthe coating. The solvent can be any suitable alcohol, includingisopropanol, polypropanol, propanol, ethanol, methanol, dimethylsulfoxide (DMSO), water and combinations of. The drying time can bebetween about 2 minutes and about 10 minutes, in some embodimentsbetween about 4 minutes and about 5 minutes. The drying temperature canbe between about 20° C. and about 50° C., in some embodiments betweenabout 27° C. and about 40° C., in some embodiments about 35° C. Thedrying time can depend on the coating thickness and solvent vaporpressure.

At least one crosslinker or network former can be used to create thecrosslinked polymer, or the networked polymer. The crosslinker can be avinyl compound (including polyvinyl ethylene glycol, polyvinyl siloxane,vinyl pyrrolidone, vinyl silanes, vinyl polyethylene oxide, and vinylpolypropylene oxide), ethyleneglycol dimethacrylate, an acrylatecompound (for example MAA), an epoxy compound, a urethane compound, anisocyanate compounds, triacrylate (for example, trimethylolpropanetriacrylate), methacrylate, methacrylic acid, and hydroxyethylmethacrylate, and combinations or two or more of these crosslinkers. Thecrosslinker can be activated by free radical or ionic mechanisms or bydehydration to produce the crosslinked polymer with an initiator. Theinitiator can be a photo or radioactive initiator, for example a UVinitiator. The wavelength to react the initiator will depend upon theinitiator properties. Initiators useful for the present inventionpreferably do not react with visible light typically found in a room ora lab as such an initiator would require additional equipment in orderto prevent the reaction from occurring prematurely. Rather, in someembodiments, the initiator can react at a wavelength less than about 280nm and a luminance between about 3 to about 5 mW/cm³. Advantageously,the initiator does not need to be attached to the crosslinker prior toreacting the crosslinker. Rather, when the initiator is used, it cansimply be added to the reaction. Furthermore, the initiator becomesactive without heat. Suitable photo initiators include1-hydroxy-cyclohexyl-phenyl-ketone (for example Ciba® IRGACURE® 184), or13-4-(2-Hydroxyethoxy)-phenyl8-2-hydroxy-2-methyl-1-propane-1-one (forexample Ciba® IRGACURE® 2959),2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, or combinationsthereof.

The crosslinkers or network formers serve at least two purposes relevantto the invention. First, the crosslinkers can be used to bond thecoating to a surface of the substrate. Second, the crosslinker can beused to entrap the hydrating polymer and/or an additive. Combinations ofmore than one crosslinkers can be utilized for a particular application.For example, a first crosslinker can be chosen based on its polarity toprovide good adhesion to a surface of a substrate. A second crosslinkercan be selected to provide lubricity to the coating and to increase thestrength of entanglement of the high molecular weight hydrating polymer.

A high molecular weight polymer can be entrapped in the crosslinkedpolymer. Suitable high molecular weight polymers will have an averagemolecular weight above about 30,000. The average molecular weight of thehigh molecular weight polymers can be between about 30,000 and about1.5M. Low molecular weight polymers would not be suitable for theinvention because they would not entrap within the crosslinked polymer.Suitable high molecular weight polymers include polyethylene oxide,polypropylene oxide, polyvinylpyrrolidone (PVP), polyvinyl alcohol, apolyacrylate, an agarose, a methylcellulose, hyaluronan, polyisocynade,polyethylene oxide, alginate, carboxymethyl cellulose, a urethanecoating, a water miscible epoxide, and the like, and combinations of twoor more of these high molecular weight polymers.

The concentration of each crosslinker components in the coating can bebetween about 0.01 wt. % and 0.5 wt. % of the total mass of the coating.When more than one crosslinker is utilized, then the total concentrationof all crosslinker components is between about 0.02 wt. % and about 2wt. % of the total mass of the coating. In some embodiments where morethan one crosslinker is utilized, the coating can include between 0.01wt. % and about 2 wt. % of a crosslinker or chain extending compound,and between about 0.01 wt. % and about 2.0 wt. % of each additionalcrosslinking or chain extending compound. The ratio of the firstcrosslinker to a second crosslinker can be between about 1:0.1 and about1:1. The concentration of the high molecular weight polymer in thecoating can be between about 3 wt. % and about 15 wt. % of the coating.The concentration of the coating solution in a solvent can be betweenabout 3 wt. % and about 15 wt. %. The solvent can be present in thecoating in an amount between about 85 wt. % and about 97 wt. %.Additives can be present in the coating in an amount between 0.05 wt. %and 0.1 wt. %. Other incidental materials (for example unreactedcomponents) can be present in the coating in an amount less than about0.1 wt. % of the total weight percent of the coating.

The thickness of the coating on the substrate can be between about 0.5microns and about 10 microns. The use of the substrate can dictate thethickness of the coating. A thickness of between about 0.5 microns andabout 10 micron can provide if the coating requires a longer dry-outtime.

In some embodiments of the invention, additives can be incorporated intothe coating. Suitable additives include antimicrobial (includingantibacterial) agents, binders, rheology modifiers, or colorants, andcombinations of two or more additives. Suitable antimicrobial agents caninclude a silver compound, chlorhexidine, ciprofloxacin, andcombinations thereof. Suitable rheology modifiers can include pluronics,alginates, carboxymethyl cellulose and combinations thereof. Suitablecolorants can include dyes or oxide pigments, and combinations thereof.The total concentration of the additives in the coating can be betweenabout 0.05 wt. % and about 0.1 wt. % of the total weight of the coating,with each additive used contributing to a portion of this total weight.

The ratio of the high molecular weight polymer to the crosslinker rangesfrom about 1:0.05 to about 1:1 for all formulations regardless of thenumber of components. The ratio of the high molecular weight polymer tothe initiator is between about 1:0.001 and about 1:01. In someembodiments, the ratio of a first crosslinker of the second crosslinkeris between about 1:0.1 and about 1:1. In some embodiments, the ratio ofa crosslinker, a high molecular weight polymer and the initiator isbetween about 1:0.1:0.005 and about 0.02:1.0:0.02.

An aspect of the invention is a method to coat a substrate. The methodincludes mixing at least one crosslinker, at least one polymer, and aninitiator to produce a pre-coating mixture. The pre-coating mixture isapplied to a substrate. Then a reaction is initiated to crosslink thecrosslinker(s) in the pre-coating mixture to produce a gradientcrosslinked coating on the substrate. The crosslinked coating entrapsthe polymer, and the gradient coating includes a variable concentrationof the crosslinker between an substrate surface of the coating and anouter surface of the coating such that the substrate surface of thegradient coating comprises a first coating polar characteristic and theouter surface of the coating comprises a second coating polarcharacteristic. The substrate surface of the coating is adjacent to theexterior surface of the substrate.

The thickness can be controlled by the concentration of the coatingsolution in the solvent, by the extraction rate used during applicationof the coating, the amount of polymer in the coating solution, or acombination of these methods to control the thickness. The thickness ofthe coating on the substrate can be between about 0.5 microns and about10 microns. For a thicker coating, a higher concentration of the coatingsolution in the solvent can be used. The higher concentration can bebetween about 5 wt. % and about 15 wt. % of the coating solution in thesolvent. For thicker coatings, the substrate can be withdrawn from thecoating solution at a faster rate compared to the rate used for athinner coating. In some embodiments, the extraction rate for a thickcoating (i.e. between about 0.5 microns and about 10 microns) can be ata rate of between 0.5 cm/s and 1 cm/s. In some embodiments, theextraction rate in general can be between about 0.2 cm/s and 1 cm/s.

The pre-coating mixture can be applied using any suitable means. Thepre-coating mixture can be applied to the substrate by dipping,spraying, painting, submerging, or other methods. The pre-coatingmixture can be applied uniformly on the substrate or can vary on thesubstrate.

The pre-coating mixture includes at least one solvent. The solvent canbe any suitable alcohol, including isopropanol, polypropanol, propanol,ethanol, methanol, dimethyl sulfoxide (DMSO), water and combinations of.The gradient can be modulated by the choice of solvent used with thecoating, the drying time (evaporation rate), temperature, and itspolarity. By decreasing the polarity with a less polar solvent, a lesspolar crosslinker or network former can disperse into the coating. Amore polar solvent can force a less polar crosslinker to the surface ofthe coating. The drying time can be between about 2 minutes and about 10minutes, in some embodiments between about 4 minutes and about 5minutes. The drying temperature can be between about 20° C. and about50° C., in some embodiments between about 27° C. and about 40° C., insome embodiments about 35° C. The drying time can depend on the coatingthickness and solvent vapor pressure.

The substrate can be contact lenses, catheters (including cardiovascularcatheters and urological catheters), wires (including guidewires),springs, leads (for example a pacemaker lead), stents, implants,antennas, sensors, tubing, syringes, catheters, i.v. bag needles,needles, ventricular assist device components, and trochars, orcombinations of two or more of these devices. The material of thesubstrate can be a polymer, a metal, a glass, polyester block amides(for example Pebax™, a silicone rubber, nylons, polyvinylchlorides,SEBs, and combinations thereof. In some embodiments, the polarcharacteristic of the exterior surface of the substrate can be alteredto assist in bonding of the coating, or to alter the stratification ofthe components based on the components polarity orhydrophobic/hydrophilic nature at the surface between the coating andthe substrate or on the exterior or outer surface of the coating. By wayof example, the polar characteristic of the exterior surface of asubstrate can be altered from hydrophobic to less hydrophobic ascompared to its initial polar characteristic, or from hydrophilic toless hydrophilic as compared to its initial polar characteristic. Whenmore than one material is used in a medical device, the polarcharacteristic of the substrate can be different at different locationscorresponding to the different materials. The medical device can be usedin contact with blood, plasma, and the like.

The polar characteristic of the substrate can result in the substratebeing hydrophobic or hydrophilic. The polar characteristic can varythrough the coating, such that the coating is hydrophobic at ansubstrate surface of the coating, gradually increasing in hydrophilicproperties to the exterior surface which is more hydrophilic, or atleast less hydrophobic, compared to the characteristic at the substratesurface of the coating. Alternatively, the polar characteristic can varythrough the coating, such that the coating is hydrophilic at ansubstrate surface of the coating, then gradually decreases inhydrophilic properties, such that the exterior surface is hydrophobic,or at least less hydrophilic, compared to the characteristic at thesubstrate surface of the coating. If more than one crosslinking materialis utilized, the additional crosslinker can also vary in a similarmanner as the first crosslinking material. For example, if a firstcrosslinker is more hydrophilic than a second crosslinker, and asubstrate is hydrophilic, the crosslinking components can align suchthat the first crosslinker is adjacent to the surface of the substrateand second crosslinker in the coating is closer to the outer surface ofthe coating. If additional crosslinkers are used in the coating, thevariation and alignment of the additional crosslinkers can be located inthe coating based on the polarity and hydrophobic/hydrophilic naturecompared to other crosslinking materials in the coating. In someembodiments when more than one crosslinker is utilized, the differentcrosslinkers can not only crosslink with other similar crosslinkers, butcan also crosslink with different crosslinkers, which can result inadditional polarities of the crosslinked material within the overallcrosslinked material.

In some embodiments, for example where only one crosslinker is utilizedin the coating, layering of the coating can be achieved based on thedensity variations in the coatings. In some embodiments, the coating canbe more dense at an substrate surface where the coating bonds orassociates to a surface of the substrate and less dense on the exteriorsurface of the coating. In other embodiments, the coating can be lessdense at an substrate surface compared to the density of the coating atan outer surface.

The polar characteristic of the coating can allow for the coating andthe substrate to create a bond. Thus, an advantage of the presentinvention is that the coating adheres to the substrate. The strength ofthe bond between the substrate and the coating can be between about 1 gmand about 500 gm. In some embodiments, when the entire substrateincludes the coating, then the coating can bond to itself forming asleeve around the substrate. The sleeve embodiment can be useful wherethe substrate is not likely to bond to the coating, but can also provideadditional strength between the coating and the substrate even when thecoating and the substrate create a bond.

The coating can be tailored for particular applications. For example, ifan application requires that the bond between the substrate and thecoating is strong, then the coating can be tailored so that it bondswith the substrate. For example, if the substrate is a polymer and theexterior surface of the polymer substrate is hydrophobic, then thecoating can be formed such that the coating exhibits a gradient wherethe hydrophobic crosslinker is close to the substrate and morehydrophilic crosslinkers are located at the surface. Embodiments of theinvention can result in the middle of the film providing additionalstrength to the coating by mono-functional network formers that haveintermediate concentration of the crosslinker that is designed to adsorbto the surface of the substrate and that of the crosslinker or networkformer selected to reside on the film surface. The vinyl polyethyleneand polypropylene oxides are such compounds which can be used as acrosslinker. Other embodiments can increase the water content of thecoating by addition of hydroxylated compounds as methacrylic acid (MAA),which can be used as a crosslinker. More than one of these embodimentscan be combined to tailor the coating for a particular application.Furthermore, it is possible to produce more than one layer or more thanone coating layers such that there are multiple layers in the coatingcreated by using the same or different coating materials on thesubstrate. In some embodiments, the coating can comprise between aboutone and about five layers, where each layer can be the same ordifferent. The coating can be on a portion of the first surface of thesubstrate such that between about 1% and about 99% of the first surfaceis coated with the coating. The coating can be on a portion of one ormore surfaces of the substrate such that between about 1% and about 99%of at least one surface of the substrate can be coated. In someembodiments, the coating can be on the entire first surface or on morethan one surface of the substrate such that it covers each surface ofthe substrate.

At least one crosslinker or network former can be used to create thecrosslinked polymer, or the networked polymer. The crosslinker can be avinyl compound (including polyvinyl ethylene glycol, polyvinyl siloxane,vinyl pyrrolidone, vinyl silanes, vinyl polyethylene oxide, and vinylpolypropylene oxide), ethyleneglycol dimethacrylate, an acrylatecompound (for example MAA), an epoxy compound, a urethane compound, anisocyanate compounds, triacrylate (for example, trimethylolpropanetriacrylate), methacrylate, methacrylic acid, and hydroxyethylmethacrylate, and combinations or two or more of these crosslinkers. Thecrosslinker can be activated by free radical or ionic mechanisms or bydehydration to produce the crosslinked polymer with an initiator. Theinitiator can be a photo or radioactive initiator, for example a UVinitiator. The wavelength to react the initiator will depend upon theinitiator properties. Initiators useful for the present inventionpreferably do not react with visible light typically found in a room ora lab as such an initiator would require additional equipment in orderto prevent the reaction from occurring prematurely. Rather, in someembodiments, the initiator can react at a wavelength less than about 280nm and a luminance between about 3 to about 5 mW/cm³. Advantageously,the initiator does not need to be attached to the crosslinker prior toreacting the crosslinker. Rather, when the initiator is used, it cansimply be added to the reaction. Furthermore, the initiator becomesactive without heat. Suitable photo initiators include1-hydroxy-cyclohexyl-phenyl-ketone (for example Ciba® IRGACURE® 184), or13-4-(2-Hydroxyethoxy)-phenyl8-2-hydroxy-2-methyl-1-propane-1-one (forexample Ciba® IRGACURE® 2959),2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, or combinationsthereof.

The crosslinkers or network formers serve at least two purposes relevantto the invention. First, the crosslinkers can be used to bond thecoating to a surface of the substrate. Second, the crosslinker can beused to entrap the hydrating polymer and/or an additive. Combinations ofmore than one crosslinkers can be utilized for a particular application.For example, a first crosslinker can be chosen based on its polarity toprovide good adhesion to a surface of a substrate. A second crosslinkercan be selected to provide lubricity to the coating and to increase thestrength of entanglement of the high molecular weight hydrating polymer.

A high molecular weight polymer can be entrapped in the crosslinkedpolymer. Suitable high molecular weight polymers will have an averagemolecular weight above about 30,000. The average molecular weight of thehigh molecular weight polymers can be between about 30,000 and about1.5M. Low molecular weight polymers would not be suitable for theinvention because they would not entrap within the crosslinked polymer.Suitable high molecular weight polymers include polyethylene oxide,polypropylene oxide, polyvinylpyrrolidone (PVP), polyvinyl alcohol, apolyacrylate, an agarose, a methylcellulose, hyaluronan, polyisocynade,polyethylene oxide, alginate, carboxymethyl cellulose, a urethanecoating, a water miscible epoxide, and the like, and combinations of twoor more of these high molecular weight polymers.

The concentration of each crosslinker components in the coating can bebetween about 0.01 wt. % and 0.5 wt. % of the total mass of the coating.When more than one crosslinker is utilized, then the total concentrationof all crosslinker components is between about 0.02 wt. % and about 2wt. % of the total mass of the coating. In some embodiments where morethan one crosslinker is utilized, the coating can include between 0.01wt. % and about 2 wt. % of a crosslinker or chain extending compound,and between about 0.01 wt. % and about 2.0 wt. % of each additionalcrosslinking or chain extending compound. The ratio of the firstcrosslinker to a second crosslinker can be between about 1:0.1 and about1:1. The concentration of the high molecular weight polymer in thecoating can be between about 3 wt. % and about 15 wt. % of the coating.The concentration of the coating solution in a solvent can be betweenabout 3 wt. % and about 15 wt. %. The solvent can be present in thecoating in an amount between about 85 wt. % and about 97 wt. %.Additives can be present in the coating in an amount between 0.05 wt. %and 0.1 wt. %. Other incidental materials (for example unreactedcomponents) can be present in the coating in an amount less than about0.1 wt. % of the total weight percent of the coating.

In some embodiments of the invention, additives can be incorporated intothe coating. Suitable additives include antimicrobial (includingantibacterial) agents, binders, rheology modifiers, or colorants, andcombinations of two or more additives. Suitable antimicrobial agents caninclude a silver compound, chlorhexidine, ciprofloxacin, andcombinations thereof. Suitable rheology modifiers can include pluronics,alginates, carboxymethyl cellulose and combinations thereof. Suitablecolorants can include dyes or oxide pigments, and combinations thereof.The total concentration of the additives in the coating can be betweenabout 0.05 wt. % and about 0.1 wt. % of the total weight of the coating,with each additive used contributing to a portion of this total weight.

The ratio of the high molecular weight polymer to the crosslinker rangesfrom about 1:0.05 to about 1:1 for all formulations regardless of thenumber of components. The ratio of the high molecular weight polymer tothe initiator is between about 1:0.001 and about 1:01. In someembodiments, the ratio of a first crosslinker of the second crosslinkeris between about 1:0.1 and about 1:1. In some embodiments, the ratio ofa crosslinker, a high molecular weight polymer and the initiator isbetween about 1:0.1:0.005 and about 0.02:1.0:0.02.

An aspect of the invention is a method to produce a pre-coating for usewith the invention. The method includes providing at least onecrosslinker, a high molecular weight polymer, and an initiator.Advantageously, the method to produce the pre-coating does not requirethe reaction to take place in a special room or contained area toprotect the molecules against premature reaction with visible light.Rather, since the present invention utilizes initiators that operateover the ultraviolet spectrum, the materials do not require specialhandling during mixture to produce the precoating.

The ratio of the crosslinking material to the polymer to the initiatorcan be between about 1:0.05 and 1:1. In some embodiments, thepre-material can be provided with an excess of initiator to drive thecrosslinking reaction to completion. The ratio of the high molecularweight polymer to the crosslinker ranges from about 1:0.05 to about 1:1for all formulations regardless of the number of components. The ratioof the high molecular weight polymer to the initiator is between about1:0.001 and about 1:01. In some embodiments, the ratio of a firstcrosslinker of the second crosslinker is between about 1:0.1 and about1:1. In some embodiments, the ratio of a crosslinker, a high molecularweight polymer and the initiator is between about 1:0.1:0.005 and about0.02:1.0:0.02.

The substrate can be contact lenses, catheters (including cardiovascularcatheters and urological catheters), wires (including guidewires),springs, leads (for example a pacemaker lead), stents, implants,antennas, sensors, tubing, syringes, catheters, i.v. bag needles,needles, ventricular assist device components, and trochars, orcombinations of two or more of these devices. The material of thesubstrate can be a polymer, a metal, a glass, polyester block amides(for example Pebax™, a silicone rubber, nylons, polyvinylchlorides,styrene ethylene butadienes (SEBs), and combinations thereof. In someembodiments, the polar characteristic of the exterior surface of thesubstrate can be altered to assist in bonding of the coating, or toalter the stratification of the components based on the componentspolarity or hydrophobic/hydrophilic nature at the surface between thecoating and the substrate or on the exterior or outer surface of thecoating. By way of example, the polar characteristic of the exteriorsurface of a substrate can be altered from hydrophobic to lesshydrophobic as compared to its initial polar characteristic, or fromhydrophilic to less hydrophilic as compared to its initial polarcharacteristic. When more than one material is used in a medical device,the polar characteristic of the substrate can be different at differentlocations corresponding to the different materials. The medical devicecan be used in contact with blood, plasma, and the like.

The polar characteristic of the substrate can result in the substratebeing hydrophobic or hydrophilic. The polar characteristic can varythrough the coating, such that the coating is hydrophobic at ansubstrate surface of the coating, gradually increasing in hydrophilicproperties to the exterior surface which is more hydrophilic, or atleast less hydrophobic, compared to the characteristic at the substratesurface of the coating. Alternatively, the polar characteristic can varythrough the coating, such that the coating is hydrophilic at ansubstrate surface of the coating, then gradually decreases inhydrophilic properties, such that the exterior surface is hydrophobic,or at least less hydrophilic, compared to the characteristic at thesubstrate surface of the coating. If more than one crosslinking materialis utilized, the additional crosslinker can also vary in a similarmanner as the first crosslinking material. For example, if a firstcrosslinker is more hydrophilic than a second crosslinker, and asubstrate is hydrophilic, the crosslinking components can align suchthat the first crosslinker is adjacent to the surface of the substrateand second crosslinker in the coating is closer to the outer surface ofthe coating. If additional crosslinkers are used in the coating, thevariation and alignment of the additional crosslinkers can be located inthe coating based on the polarity and hydrophobic/hydrophilic naturecompared to other crosslinking materials in the coating. In someembodiments when more than one crosslinker is utilized, the differentcrosslinkers can not only crosslink with other similar crosslinkers, butcan also crosslink with different crosslinkers, which can result inadditional polarities of the crosslinked material within the overallcrosslinked material.

In some embodiments, for example where only one crosslinker is utilizedin the coating, layering of the coating can be achieved based on thedensity variations in the coatings. In some embodiments, the coating canbe more dense at an substrate surface where the coating bonds orassociates to a surface of the substrate and less dense on the exteriorsurface of the coating. In other embodiments, the coating can be lessdense at an substrate surface compared to the density of the coating atan outer surface.

The polar characteristic of the coating can allow for the coating andthe substrate to create a bond. Thus, an advantage of the presentinvention is that the coating adheres to the substrate. The strength ofthe bond between the substrate and the coating can be between about 1 gmand about 500 gm. In some embodiments, when the entire substrateincludes the coating, then the coating can bond to itself forming asleeve around the substrate. The sleeve embodiment can be useful wherethe substrate is not likely to bond to the coating, but can also provideadditional strength between the coating and the substrate even when thecoating and the substrate create a bond.

The coating can be tailored for particular applications. For example, ifan application requires that the bond between the substrate and thecoating is strong, then the coating can be tailored so that it bondswith the substrate. For example, if the substrate is a polymer and theexterior surface of the polymer substrate is hydrophobic, then thecoating can be formed such that the coating exhibits a gradient wherethe hydrophobic crosslinker is close to the substrate and morehydrophilic crosslinkers are located at the surface. Embodiments of theinvention can result in the middle of the film providing additionalstrength to the coating by mono-functional network formers that haveintermediate concentration of the crosslinker that is designed to adsorbto the surface of the substrate and that of the crosslinker or networkformer selected to reside on the film surface. The vinyl polyethyleneand polypropylene oxides are such compounds which can be used as acrosslinker. Other embodiments can increase the water content of thecoating by addition of hydroxylated compounds as methacrylic acid (MAA),which can be used as a crosslinker. More than one of these embodimentscan be combined to tailor the coating for a particular application.Furthermore, it is possible to produce more than one layer or more thanone coating layers such that there are multiple layers in the coatingcreated by using the same or different coating materials on thesubstrate. In some embodiments, the coating can comprise between aboutone and about five layers, where each layer can be the same ordifferent. The coating can be on a portion of the first surface of thesubstrate such that between about 1% and about 99% of the first surfaceis coated with the coating. The coating can be on a portion of one ormore surfaces of the substrate such that between about 1% and about 99%of at least one surface of the substrate can be coated. In someembodiments, the coating can be on the entire first surface or on morethan one surface of the substrate such that it covers each surface ofthe substrate.

The gradient can be modulated by the choice of solvent used with thecoating, the drying time (evaporation rate), temperature, and itspolarity. By decreasing the polarity with a less polar solvent, a lesspolar crosslinker or network former can disperse into the coating. Amore polar solvent can force a less polar crosslinker to the surface ofthe coating. The solvent can be any suitable alcohol, includingisopropanol, polypropanol, propanol, ethanol, methanol, dimethylsulfoxide (DMSO), water and combinations of. The drying time can bebetween about 2 minutes and about 10 minutes, in some embodimentsbetween about 4 minutes and about 5 minutes. The drying temperature canbe between about 20° C. and about 50° C., in some embodiments betweenabout 27° C. and about 40° C., in some embodiments about 35° C. Thedrying time can depend on the coating thickness and solvent vaporpressure.

At least one crosslinker or network former can be used to create thecrosslinked polymer, or the networked polymer. The crosslinker can be avinyl compound (including polyvinyl ethylene glycol, polyvinyl siloxane,vinyl pyrrolidone, vinyl silanes, vinyl polyethylene oxide, and vinylpolypropylene oxide), ethyleneglycol dimethacrylate, an acrylatecompound (for example MAA), an epoxy compound, a urethane compound, anisocyanate compounds, triacrylate (for example, trimethylolpropanetriacrylate), methacrylate, methacrylic acid, and hydroxyethylmethacrylate, and combinations or two or more of these crosslinkers. Thecrosslinker can be activated by free radical or ionic mechanisms or bydehydration to produce the crosslinked polymer with an initiator. Theinitiator can be a photo or radioactive initiator, for example a UVinitiator. The wavelength to react the initiator will depend upon theinitiator properties. Initiators useful for the present inventionpreferably do not react with visible light typically found in a room ora lab as such an initiator would require additional equipment in orderto prevent the reaction from occurring prematurely. Rather, in someembodiments, the initiator can react at a wavelength less than about 280nm and a luminance between about 3 to about 5 mW/cm³. Advantageously,the initiator does not need to be attached to the crosslinker prior toreacting the crosslinker. Rather, when the initiator is used, it cansimply be added to the reaction. Furthermore, the initiator becomesactive without heat. Suitable photo initiators include1-hydroxy-cyclohexyl-phenyl-ketone (for example Ciba® IRGACURE® 184), or13-4-(2-Hydroxyethoxy)-phenyl8-2-hydroxy-2-methyl-1-propane-1-one (forexample Ciba® IRGACURE® 2959),2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, or combinationsthereof.

The crosslinkers or network formers serve at least two purposes relevantto the invention. First, the crosslinkers can be used to bond thecoating to a surface of the substrate. Second, the crosslinker can beused to entrap the hydrating polymer and/or an additive. Combinations ofmore than one crosslinkers can be utilized for a particular application.For example, a first crosslinker can be chosen based on its polarity toprovide good adhesion to a surface of a substrate. A second crosslinkercan be selected to provide lubricity to the coating and to increase thestrength of entanglement of the high molecular weight hydrating polymer.

A high molecular weight polymer can be entrapped in the crosslinkedpolymer. Suitable high molecular weight polymers will have an averagemolecular weight above about 30,000. The average molecular weight of thehigh molecular weight polymers can be between about 30,000 and about1.5M. Low molecular weight polymers would not be suitable for theinvention because they would not entrap within the crosslinked polymer.Suitable high molecular weight polymers include polyethylene oxide,polypropylene oxide, polyvinylpyrrolidone (PVP), polyvinyl alcohol, apolyacrylate, an agarose, a methylcellulose, hyaluronan, polyisocynade,polyethylene oxide, alginate, carboxymethyl cellulose, a urethanecoating, a water miscible epoxide, and the like, and combinations of twoor more of these high molecular weight polymers.

The concentration of each crosslinker components in the coating can bebetween about 0.01 wt. % and 0.5 wt. % of the total mass of the coating.When more than one crosslinker is utilized, then the total concentrationof all crosslinker components is between about 0.02 wt. % and about 2wt. % of the total mass of the coating. In some embodiments where morethan one crosslinker is utilized, the coating can include between 0.01wt. % and about 2 wt. % of a crosslinker or chain extending compound,and between about 0.01 wt. % and about 2.0 wt. % of each additionalcrosslinking or chain extending compound. The ratio of the firstcrosslinker to a second crosslinker can be between about 1:0.1 and about1:1. The concentration of the high molecular weight polymer in thecoating can be between about 3 wt. % and about 15 wt. % of the coating.The concentration of the coating solution in a solvent can be betweenabout 3 wt. % and about 15 wt. %. The solvent can be present in thecoating in an amount between about 85 wt. % and about 97 wt. %.Additives can be present in the coating in an amount between 0.05 wt. %and 0.1 wt. %. Other incidental materials (for example unreactedcomponents) can be present in the coating in an amount less than about0.1 wt. % of the total weight percent of the coating.

The thickness of the coating on the substrate can be between about 0.5microns and about 10 microns. The use of the substrate can dictate thethickness of the coating. A thickness of between about 0.5 microns andabout 10 micron can provide if the coating requires a longer dry-outtime.

In some embodiments of the invention, additives can be incorporated intothe coating. Suitable additives include antimicrobial (includingantibacterial) agents, binders, rheology modifiers, or colorants, andcombinations of two or more additives. Suitable antimicrobial agents caninclude a silver compound, chlorhexidine, ciprofloxacin, andcombinations thereof. Suitable rheology modifiers can include pluronics,alginates, carboxymethyl cellulose and combinations thereof. Suitablecolorants can include dyes or oxide pigments, and combinations thereof.The total concentration of the additives in the coating can be betweenabout 0.05 wt. % and about 0.1 wt. % of the total weight of the coating,with each additive used contributing to a portion of this total weight.

An aspect of the invention is a pre-coating material for use on amedical device. The coating includes at least one crosslinker, and apolymer. An initiator is used to crosslink a crosslinking agent, but theinitiator is not attached to the crosslinker. The coating provides agradient concentration of the crosslinker when applied to a substrate.

The substrate can be contact lenses, catheters (including cardiovascularcatheters and urological catheters), wires (including guidewires),springs, leads (for example a pacemaker lead), stents, implants,antennas, sensors, tubing, syringes, catheters, i.v. bag needles,needles, ventricular assist device components, and trochars, orcombinations of two or more of these devices. The material of thesubstrate can be a polymer, a metal, a glass, polyester block amides(for example Pebax™, a silicone rubber, nylons, polyvinylchlorides,styrene ethylene butadienes (SEBs), and combinations thereof. In someembodiments, the polar characteristic of the exterior surface of thesubstrate can be altered to assist in bonding of the coating, or toalter the stratification of the components based on the componentspolarity or hydrophobic/hydrophilic nature at the surface between thecoating and the substrate or on the exterior or outer surface of thecoating. By way of example, the polar characteristic of the exteriorsurface of a substrate can be altered from hydrophobic to lesshydrophobic as compared to its initial polar characteristic, or fromhydrophilic to less hydrophilic as compared to its initial polarcharacteristic. When more than one material is used in a medical device,the polar characteristic of the substrate can be different at differentlocations corresponding to the different materials. The medical devicecan be used in contact with blood, plasma, and the like.

The polar characteristic of the substrate can result in the substratebeing hydrophobic or hydrophilic. The polar characteristic can varythrough the coating, such that the coating is hydrophobic at ansubstrate surface of the coating, gradually increasing in hydrophilicproperties to the exterior surface which is more hydrophilic, or atleast less hydrophobic, compared to the characteristic at the substratesurface of the coating. Alternatively, the polar characteristic can varythrough the coating, such that the coating is hydrophilic at ansubstrate surface of the coating, then gradually decreases inhydrophilic properties, such that the exterior surface is hydrophobic,or at least less hydrophilic, compared to the characteristic at thesubstrate surface of the coating. If more than one crosslinking materialis utilized, the additional crosslinker can also vary in a similarmanner as the first crosslinking material. For example, if a firstcrosslinker is more hydrophilic than a second crosslinker, and asubstrate is hydrophilic, the crosslinking components can align suchthat the first crosslinker is adjacent to the surface of the substrateand second crosslinker in the coating is closer to the outer surface ofthe coating. If additional crosslinkers are used in the coating, thevariation and alignment of the additional crosslinkers can be located inthe coating based on the polarity and hydrophobic/hydrophilic naturecompared to other crosslinking materials in the coating. In someembodiments when more than one crosslinker is utilized, the differentcrosslinkers can not only crosslink with other similar crosslinkers, butcan also crosslink with different crosslinkers, which can result inadditional polarities of the crosslinked material within the overallcrosslinked material.

In some embodiments, for example where only one crosslinker is utilizedin the coating, layering of the coating can be achieved based on thedensity variations in the coatings. In some embodiments, the coating canbe more dense at an substrate surface where the coating bonds orassociates to a surface of the substrate and less dense on the exteriorsurface of the coating. In other embodiments, the coating can be lessdense at an substrate surface compared to the density of the coating atan outer surface.

The polar characteristic of the coating can allow for the coating andthe substrate to create a bond. Thus, an advantage of the presentinvention is that the coating adheres to the substrate. The strength ofthe bond between the substrate and the coating can be between about 1 gmand about 500 gm. In some embodiments, when the entire substrateincludes the coating, then the coating can bond to itself forming asleeve around the substrate. The sleeve embodiment can be useful wherethe substrate is not likely to bond to the coating, but can also provideadditional strength between the coating and the substrate even when thecoating and the substrate create a bond.

The coating can be tailored for particular applications. For example, ifan application requires that the bond between the substrate and thecoating is strong, then the coating can be tailored so that it bondswith the substrate. For example, if the substrate is a polymer and theexterior surface of the polymer substrate is hydrophobic, then thecoating can be formed such that the coating exhibits a gradient wherethe hydrophobic crosslinker is close to the substrate and morehydrophilic crosslinkers are located at the surface. Embodiments of theinvention can result in the middle of the film providing additionalstrength to the coating by mono-functional network formers that haveintermediate concentration of the crosslinker that is designed to adsorbto the surface of the substrate and that of the crosslinker or networkformer selected to reside on the film surface. The vinyl polyethyleneand polypropylene oxides are such compounds which can be used as acrosslinker. Other embodiments can increase the water content of thecoating by addition of hydroxylated compounds as methacrylic acid (MAA),which can be used as a crosslinker. More than one of these embodimentscan be combined to tailor the coating for a particular application.Furthermore, it is possible to produce more than one layer or more thanone coating layers such that there are multiple layers in the coatingcreated by using the same or different coating materials on thesubstrate. In some embodiments, the coating can comprise between aboutone and about five layers, where each layer can be the same ordifferent. The coating can be on a portion of the first surface of thesubstrate such that between about 1% and about 99% of the first surfaceis coated with the coating. The coating can be on a portion of one ormore surfaces of the substrate such that between about 1% and about 99%of at least one surface of the substrate can be coated. In someembodiments, the coating can be on the entire first surface or on morethan one surface of the substrate such that it covers each surface ofthe substrate.

The gradient can be modulated by the choice of solvent used with thecoating, the drying time (evaporation rate), temperature, and itspolarity. By decreasing the polarity with a less polar solvent, a lesspolar crosslinker or network former can disperse into the coating. Amore polar solvent can force a less polar crosslinker to the surface ofthe coating. The solvent can be any suitable alcohol, includingisopropanol, polypropanol, propanol, ethanol, methanol, dimethylsulfoxide (DMSO), water and combinations of. The drying time can bebetween about 2 minutes and about 10 minutes, in some embodimentsbetween about 4 minutes and about 5 minutes. The drying temperature canbe between about 20° C. and about 50° C., in some embodiments betweenabout 27° C. and about 40° C., in some embodiments about 35° C. Thedrying time can depend on the coating thickness and solvent vaporpressure.

At least one crosslinker or network former can be used to create thecrosslinked polymer, or the networked polymer. The crosslinker can be avinyl compound (including polyvinyl ethylene glycol, polyvinyl siloxane,vinyl pyrrolidone, vinyl silanes, vinyl polyethylene oxide, and vinylpolypropylene oxide), ethyleneglycol dimethacrylate, an acrylatecompound (for example MAA), an epoxy compound, a urethane compound, anisocyanate compounds, triacrylate (for example, trimethylolpropanetriacrylate), methacrylate, methacrylic acid, and hydroxyethylmethacrylate, and combinations or two or more of these crosslinkers. Thecrosslinker can be activated by free radical or ionic mechanisms or bydehydration to produce the crosslinked polymer with an initiator. Theinitiator can be a photo or radioactive initiator, for example a UVinitiator. The wavelength to react the initiator will depend upon theinitiator properties. Initiators useful for the present inventionpreferably do not react with visible light typically found in a room ora lab as such an initiator would require additional equipment in orderto prevent the reaction from occurring prematurely. Rather, in someembodiments, the initiator can react at a wavelength less than about 280nm and a luminance between about 3 to about 5 mW/cm³. Advantageously,the initiator does not need to be attached to the crosslinker prior toreacting the crosslinker. Rather, when the initiator is used, it cansimply be added to the reaction. Furthermore, the initiator becomesactive without heat. Suitable photo initiators include1-hydroxy-cyclohexyl-phenyl-ketone (for example Ciba® IRGACURE® 184), or13-4-(2-Hydroxyethoxy)-phenyl8-2-hydroxy-2-methyl-1-propane-1-one (forexample Ciba® IRGACURE® 2959),2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, or combinationsthereof.

The crosslinkers or network formers serve at least two purposes relevantto the invention. First, the crosslinkers can be used to bond thecoating to a surface of the substrate. Second, the crosslinker can beused to entrap the hydrating polymer and/or an additive. Combinations ofmore than one crosslinkers can be utilized for a particular application.For example, a first crosslinker can be chosen based on its polarity toprovide good adhesion to a surface of a substrate. A second crosslinkercan be selected to provide lubricity to the coating and to increase thestrength of entanglement of the high molecular weight hydrating polymer.

A high molecular weight polymer can be entrapped in the crosslinkedpolymer. Suitable high molecular weight polymers will have an averagemolecular weight above about 30,000. The average molecular weight of thehigh molecular weight polymers can be between about 30,000 and about1.5M. Low molecular weight polymers would not be suitable for theinvention because they would not entrap within the crosslinked polymer.Suitable high molecular weight polymers include polyethylene oxide,polypropylene oxide, polyvinylpyrrolidone (PVP), polyvinyl alcohol, apolyacrylate, an agarose, a methylcellulose, hyaluronan, polyisocynade,polyethylene oxide, alginate, carboxymethyl cellulose, a urethanecoating, a water miscible epoxide, and the like, and combinations of twoor more of these high molecular weight polymers.

The concentration of each crosslinker components in the coating can bebetween about 0.01 wt. % and 0.5 wt. % of the total mass of the coating.When more than one crosslinker is utilized, then the total concentrationof all crosslinker components is between about 0.02 wt. % and about 2wt. % of the total mass of the coating. In some embodiments where morethan one crosslinker is utilized, the coating can include between 0.01wt. % and about 2 wt. % of a crosslinker or chain extending compound,and between about 0.01 wt. % and about 2.0 wt. % of each additionalcrosslinking or chain extending compound. The ratio of the firstcrosslinker to a second crosslinker can be between about 1:0.1 and about1:1. The concentration of the high molecular weight polymer in thecoating can be between about 3 wt. % and about 15 wt. % of the coating.The concentration of the coating solution in a solvent can be betweenabout 3 wt. % and about 15 wt. %. The solvent can be present in thecoating in an amount between about 85 wt. % and about 97 wt. %.Additives can be present in the coating in an amount between 0.05 wt. %and 0.1 wt. %. Other incidental materials (for example unreactedcomponents) can be present in the coating in an amount less than about0.1 wt. % of the total weight percent of the coating.

The thickness of the coating on the substrate can be between about 0.5microns and about 10 microns. The use of the substrate can dictate thethickness of the coating. A thickness of between about 0.5 microns andabout 10 micron can provide if the coating requires a longer dry-outtime.

In some embodiments of the invention, additives can be incorporated intothe coating. Suitable additives include antimicrobial (includingantibacterial) agents, binders, rheology modifiers, or colorants, andcombinations of two or more additives. Suitable antimicrobial agents caninclude a silver compound, chlorhexidine, ciprofloxacin, andcombinations thereof. Suitable rheology modifiers can include pluronics,alginates, carboxymethyl cellulose and combinations thereof. Suitablecolorants can include dyes or oxide pigments, and combinations thereof.The total concentration of the additives in the coating can be betweenabout 0.05 wt. % and about 0.1 wt. % of the total weight of the coating,with each additive used contributing to a portion of this total weight.

An aspect of the invention is a coating for use on a medical device. Thecoating includes at least one network former or one crosslinked polymer,and a high molecular weight polymer, and less than about 0.01 wt. % ofincidental materials. The coating provides a gradient density whenapplied to a substrate. The gradient is generated primarily by thenetwork former or crosslinking components.

The substrate can be contact lenses, catheters (including cardiovascularcatheters and urological catheters), wires (including guidewires),springs, leads (for example a pacemaker lead), stents, implants,antennas, sensors, tubing, syringes, catheters, i.v. bag needles,needles, ventricular assist device components, and trochars, orcombinations of two or more of these devices. The material of thesubstrate can be a polymer, a metal, a glass, polyester block amides(for example Pebax™, a silicone rubber, nylons, polyvinylchlorides,styrene ethylene butadienes (SEBs), and combinations thereof. In someembodiments, the polar characteristic of the exterior surface of thesubstrate can be altered to assist in bonding of the coating, or toalter the stratification of the components based on the componentspolarity or hydrophobic/hydrophilic nature at the surface between thecoating and the substrate or on the exterior or outer surface of thecoating. By way of example, the polar characteristic of the exteriorsurface of a substrate can be altered from hydrophobic to lesshydrophobic as compared to its initial polar characteristic, or fromhydrophilic to less hydrophilic as compared to its initial polarcharacteristic. When more than one material is used in a medical device,the polar characteristic of the substrate can be different at differentlocations corresponding to the different materials. The medical devicecan be used in contact with blood, plasma, and the like.

The polar characteristic of the substrate can result in the substratebeing hydrophobic or hydrophilic. The polar characteristic can varythrough the coating, such that the coating is hydrophobic at ansubstrate surface of the coating, gradually increasing in hydrophilicproperties to the exterior surface which is more hydrophilic, or atleast less hydrophobic, compared to the characteristic at the substratesurface of the coating. Alternatively, the polar characteristic can varythrough the coating, such that the coating is hydrophilic at ansubstrate surface of the coating, then gradually decreases inhydrophilic properties, such that the exterior surface is hydrophobic,or at least less hydrophilic, compared to the characteristic at thesubstrate surface of the coating. If more than one crosslinking materialis utilized, the additional crosslinker can also vary in a similarmanner as the first crosslinking material. For example, if a firstcrosslinker is more hydrophilic than a second crosslinker, and asubstrate is hydrophilic, the crosslinking components can align suchthat the first crosslinker is adjacent to the surface of the substrateand second crosslinker in the coating is closer to the outer surface ofthe coating. If additional crosslinkers are used in the coating, thevariation and alignment of the additional crosslinkers can be located inthe coating based on the polarity and hydrophobic/hydrophilic naturecompared to other crosslinking materials in the coating. In someembodiments when more than one crosslinker is utilized, the differentcrosslinkers can not only crosslink with other similar crosslinkers, butcan also crosslink with different crosslinkers, which can result inadditional polarities of the crosslinked material within the overallcrosslinked material.

In some embodiments, for example where only one crosslinker is utilizedin the coating, layering of the coating can be achieved based on thedensity variations in the coatings. In some embodiments, the coating canbe more dense at an substrate surface where the coating bonds orassociates to a surface of the substrate and less dense on the exteriorsurface of the coating. In other embodiments, the coating can be lessdense at an substrate surface compared to the density of the coating atan outer surface.

The polar characteristic of the coating can allow for the coating andthe substrate to create a bond. Thus, an advantage of the presentinvention is that the coating adheres to the substrate. The strength ofthe bond between the substrate and the coating can be between about 1 gmand about 500 gm. In some embodiments, when the entire substrateincludes the coating, then the coating can bond to itself forming asleeve around the substrate. The sleeve embodiment can be useful wherethe substrate is not likely to bond to the coating, but can also provideadditional strength between the coating and the substrate even when thecoating and the substrate create a bond.

The coating can be tailored for particular applications. For example, ifan application requires that the bond between the substrate and thecoating is strong, then the coating can be tailored so that it bondswith the substrate. For example, if the substrate is a polymer and theexterior surface of the polymer substrate is hydrophobic, then thecoating can be formed such that the coating exhibits a gradient wherethe hydrophobic crosslinker is close to the substrate and morehydrophilic crosslinkers are located at the surface. Embodiments of theinvention can result in the middle of the film providing additionalstrength to the coating by mono-functional network formers that haveintermediate concentration of the crosslinker that is designed to adsorbto the surface of the substrate and that of the crosslinker or networkformer selected to reside on the film surface. The vinyl polyethyleneand polypropylene oxides are such compounds which can be used as acrosslinker. Other embodiments can increase the water content of thecoating by addition of hydroxylated compounds as methacrylic acid (MAA),which can be used as a crosslinker. More than one of these embodimentscan be combined to tailor the coating for a particular application.Furthermore, it is possible to produce more than one layer or more thanone coating layers such that there are multiple layers in the coatingcreated by using the same or different coating materials on thesubstrate. In some embodiments, the coating can comprise between aboutone and about five layers, where each layer can be the same ordifferent. The coating can be on a portion of the first surface of thesubstrate such that between about 1% and about 99% of the first surfaceis coated with the coating. The coating can be on a portion of one ormore surfaces of the substrate such that between about 1% and about 99%of at least one surface of the substrate can be coated. In someembodiments, the coating can be on the entire first surface or on morethan one surface of the substrate such that it covers each surface ofthe substrate.

The gradient can be modulated by the choice of solvent used with thecoating, the drying time (evaporation rate), temperature, and itspolarity. By decreasing the polarity with a less polar solvent, a lesspolar crosslinker or network former can disperse into the coating. Amore polar solvent can force a less polar crosslinker to the surface ofthe coating. The solvent can be any suitable alcohol, includingisopropanol, polypropanol, propanol, ethanol, methanol, dimethylsulfoxide (DMSO), water and combinations of. The drying time can bebetween about 2 minutes and about 10 minutes, in some embodimentsbetween about 4 minutes and about 5 minutes. The drying temperature canbe between about 20° C. and about 50° C., in some embodiments betweenabout 27° C. and about 40° C., in some embodiments about 35° C. Thedrying time can depend on the coating thickness and solvent vaporpressure.

At least one crosslinker or network former can be used to create thecrosslinked polymer, or the networked polymer. The crosslinker can be avinyl compound (including polyvinyl ethylene glycol, polyvinyl siloxane,vinyl pyrrolidone, vinyl silanes, vinyl polyethylene oxide, and vinylpolypropylene oxide), ethyleneglycol dimethacrylate, an acrylatecompound (for example MAA), an epoxy compound, a urethane compound, anisocyanate compounds, triacrylate (for example, trimethylolpropanetriacrylate), methacrylate, methacrylic acid, and hydroxyethylmethacrylate, and combinations or two or more of these crosslinkers. Thecrosslinker can be activated by free radical or ionic mechanisms or bydehydration to produce the crosslinked polymer with an initiator. Theinitiator can be a photo or radioactive initiator, for example a UVinitiator. The wavelength to react the initiator will depend upon theinitiator properties. Initiators useful for the present inventionpreferably do not react with visible light typically found in a room ora lab as such an initiator would require additional equipment in orderto prevent the reaction from occurring prematurely. Rather, in someembodiments, the initiator can react at a wavelength less than about 280nm and a luminance between about 3 to about 5 mW/cm³. Advantageously,the initiator does not need to be attached to the crosslinker prior toreacting the crosslinker. Rather, when the initiator is used, it cansimply be added to the reaction. Furthermore, the initiator becomesactive without heat. Suitable photo initiators include1-hydroxy-cyclohexyl-phenyl-ketone (for example Ciba® IRGACURE® 184), or13-4-(2-Hydroxyethoxy)-phenyl8-2-hydroxy-2-methyl-1-propane-1-one (forexample Ciba® IRGACURE® 2959),2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, or combinationsthereof.

The crosslinkers or network formers serve at least two purposes relevantto the invention. First, the crosslinkers can be used to bond thecoating to a surface of the substrate. Second, the crosslinker can beused to entrap the hydrating polymer and/or an additive. Combinations ofmore than one crosslinkers can be utilized for a particular application.For example, a first crosslinker can be chosen based on its polarity toprovide good adhesion to a surface of a substrate. A second crosslinkercan be selected to provide lubricity to the coating and to increase thestrength of entanglement of the high molecular weight hydrating polymer.

A high molecular weight polymer can be entrapped in the crosslinkedpolymer. Suitable high molecular weight polymers will have an averagemolecular weight above about 30,000. The average molecular weight of thehigh molecular weight polymers can be between about 30,000 and about1.5M. Low molecular weight polymers would not be suitable for theinvention because they would not entrap within the crosslinked polymer.Suitable high molecular weight polymers include polyethylene oxide,polypropylene oxide, polyvinylpyrrolidone (PVP), polyvinyl alcohol, apolyacrylate, an agarose, a methylcellulose, hyaluronan, polyisocynade,polyethylene oxide, alginate, carboxymethyl cellulose, a urethanecoating, a water miscible epoxide, and the like, and combinations of twoor more of these high molecular weight polymers.

The concentration of each crosslinker components in the coating can bebetween about 0.01 wt. % and 0.5 wt. % of the total mass of the coating.When more than one crosslinker is utilized, then the total concentrationof all crosslinker components is between about 0.02 wt. % and about 2wt. % of the total mass of the coating. In some embodiments where morethan one crosslinker is utilized, the coating can include between 0.01wt. % and about 2 wt. % of a crosslinker or chain extending compound,and between about 0.01 wt. % and about 2.0 wt. % of each additionalcrosslinking or chain extending compound. The ratio of the firstcrosslinker to a second crosslinker can be between about 1:0.1 and about1:1. The concentration of the high molecular weight polymer in thecoating can be between about 3 wt. % and about 15 wt. % of the coating.The concentration of the coating solution in a solvent can be betweenabout 3 wt. % and about 15 wt. %. The solvent can be present in thecoating in an amount between about 85 wt. % and about 97 wt. %.Additives can be present in the coating in an amount between 0.05 wt. %and 0.1 wt. %. Other incidental materials (for example unreactedcomponents) can be present in the coating in an amount less than about0.1 wt. % of the total weight percent of the coating.

The thickness of the coating on the substrate can be between about 0.5microns and about 10 microns. The use of the substrate can dictate thethickness of the coating. A thickness of between about 0.5 microns andabout 10 micron can provide if the coating requires a longer dry-outtime.

In some embodiments of the invention, additives can be incorporated intothe coating. Suitable additives include antimicrobial (includingantibacterial) agents, binders, rheology modifiers, or colorants, andcombinations of two or more additives. Suitable antimicrobial agents caninclude a silver compound, chlorhexidine, ciprofloxacin, andcombinations thereof. Suitable rheology modifiers can include pluronics,alginates, carboxymethyl cellulose and combinations thereof. Suitablecolorants can include dyes or oxide pigments, and combinations thereof.The total concentration of the additives in the coating can be betweenabout 0.05 wt. % and about 0.1 wt. % of the total weight of the coating,with each additive used contributing to a portion of this total weight.

An aspect of the invention is a pre-coating material for use on amedical device. The coating includes at least two crosslinkers, and atleast one polymer. An initiator is used to crosslink the crosslinkersand entrap the polymer, but the initiator is not attached to thecrosslinker. The crosslinked coating provides a gradient concentrationwhen applied to a substrate.

The substrate can be contact lenses, catheters (including cardiovascularcatheters and urological catheters), wires (including guidewires),springs, leads (for example a pacemaker lead), stents, implants,antennas, sensors, tubing, syringes, catheters, i.v. bag needles,needles, ventricular assist device components, and trochars, orcombinations of two or more of these devices. The material of thesubstrate can be a polymer, a metal, a glass, polyester block amides(for example Pebax™, a silicone rubber, nylons, polyvinylchlorides,styrene ethylene butadienes (SEBs), and combinations thereof. In someembodiments, the polar characteristic of the exterior surface of thesubstrate can be altered to assist in bonding of the coating, or toalter the stratification of the components based on the componentspolarity or hydrophobic/hydrophilic nature at the surface between thecoating and the substrate or on the exterior or outer surface of thecoating. By way of example, the polar characteristic of the exteriorsurface of a substrate can be altered from hydrophobic to lesshydrophobic as compared to its initial polar characteristic, or fromhydrophilic to less hydrophilic as compared to its initial polarcharacteristic. When more than one material is used in a medical device,the polar characteristic of the substrate can be different at differentlocations corresponding to the different materials. The medical devicecan be used in contact with blood, plasma, and the like.

The polar characteristic of the substrate can result in the substratebeing hydrophobic or hydrophilic. The polar characteristic can varythrough the coating, such that the coating is hydrophobic at ansubstrate surface of the coating, gradually increasing in hydrophilicproperties to the exterior surface which is more hydrophilic, or atleast less hydrophobic, compared to the characteristic at the substratesurface of the coating. Alternatively, the polar characteristic can varythrough the coating, such that the coating is hydrophilic at ansubstrate surface of the coating, then gradually decreases inhydrophilic properties, such that the exterior surface is hydrophobic,or at least less hydrophilic, compared to the characteristic at thesubstrate surface of the coating. If more than one crosslinking materialis utilized, the additional crosslinker can also vary in a similarmanner as the first crosslinking material. For example, if a firstcrosslinker is more hydrophilic than a second crosslinker, and asubstrate is hydrophilic, the crosslinking components can align suchthat the first crosslinker is adjacent to the surface of the substrateand second crosslinker in the coating is closer to the outer surface ofthe coating. If additional crosslinkers are used in the coating, thevariation and alignment of the additional crosslinkers can be located inthe coating based on the polarity and hydrophobic/hydrophilic naturecompared to other crosslinking materials in the coating. In someembodiments when more than one crosslinker is utilized, the differentcrosslinkers can not only crosslink with other similar crosslinkers, butcan also crosslink with different crosslinkers, which can result inadditional polarities of the crosslinked material within the overallcrosslinked material.

In some embodiments, for example where only one crosslinker is utilizedin the coating, layering of the coating can be achieved based on thedensity variations in the coatings. In some embodiments, the coating canbe more dense at an substrate surface where the coating bonds orassociates to a surface of the substrate and less dense on the exteriorsurface of the coating. In other embodiments, the coating can be lessdense at an substrate surface compared to the density of the coating atan outer surface.

The polar characteristic of the coating can allow for the coating andthe substrate to create a bond. Thus, an advantage of the presentinvention is that the coating adheres to the substrate. The strength ofthe bond between the substrate and the coating can be between about 1 gmand about 500 gm. In some embodiments, when the entire substrateincludes the coating, then the coating can bond to itself forming asleeve around the substrate. The sleeve embodiment can be useful wherethe substrate is not likely to bond to the coating, but can also provideadditional strength between the coating and the substrate even when thecoating and the substrate create a bond.

The coating can be tailored for particular applications. For example, ifan application requires that the bond between the substrate and thecoating is strong, then the coating can be tailored so that it bondswith the substrate. For example, if the substrate is a polymer and theexterior surface of the polymer substrate is hydrophobic, then thecoating can be formed such that the coating exhibits a gradient wherethe hydrophobic crosslinker is close to the substrate and morehydrophilic crosslinkers are located at the surface. Embodiments of theinvention can result in the middle of the film providing additionalstrength to the coating by mono-functional network formers that haveintermediate concentration of the crosslinker that is designed to adsorbto the surface of the substrate and that of the crosslinker or networkformer selected to reside on the film surface. The vinyl polyethyleneand polypropylene oxides are such compounds which can be used as acrosslinker. Other embodiments can increase the water content of thecoating by addition of hydroxylated compounds as methacrylic acid (MAA),which can be used as a crosslinker. More than one of these embodimentscan be combined to tailor the coating for a particular application.Furthermore, it is possible to produce more than one layer or more thanone coating layers such that there are multiple layers in the coatingcreated by using the same or different coating materials on thesubstrate. In some embodiments, the coating can comprise between aboutone and about five layers, where each layer can be the same ordifferent. The coating can be on a portion of the first surface of thesubstrate such that between about 1% and about 99% of the first surfaceis coated with the coating. The coating can be on a portion of one ormore surfaces of the substrate such that between about 1% and about 99%of at least one surface of the substrate can be coated. In someembodiments, the coating can be on the entire first surface or on morethan one surface of the substrate such that it covers each surface ofthe substrate.

The gradient can be modulated by the choice of solvent used with thecoating, the drying time (evaporation rate), temperature, and itspolarity. By decreasing the polarity with a less polar solvent, a lesspolar crosslinker or network former can disperse into the coating. Amore polar solvent can force a less polar crosslinker to the surface ofthe coating. The solvent can be any suitable alcohol, includingisopropanol, polypropanol, propanol, ethanol, methanol, dimethylsulfoxide (DMSO), water and combinations of. The drying time can bebetween about 2 minutes and about 10 minutes, in some embodimentsbetween about 4 minutes and about 5 minutes. The drying temperature canbe between about 20° C. and about 50° C., in some embodiments betweenabout 27° C. and about 40° C., in some embodiments about 35° C. Thedrying time can depend on the coating thickness and solvent vaporpressure.

At least one crosslinker or network former can be used to create thecrosslinked polymer, or the networked polymer. The crosslinker can be avinyl compound (including polyvinyl ethylene glycol, polyvinyl siloxane,vinyl pyrrolidone, vinyl silanes, vinyl polyethylene oxide, and vinylpolypropylene oxide), ethyleneglycol dimethacrylate, an acrylatecompound (for example MAA), an epoxy compound, a urethane compound, anisocyanate compounds, triacrylate (for example, trimethylolpropanetriacrylate), methacrylate, methacrylic acid, and hydroxyethylmethacrylate, and combinations or two or more of these crosslinkers. Thecrosslinker can be activated by free radical or ionic mechanisms or bydehydration to produce the crosslinked polymer with an initiator. Theinitiator can be a photo or radioactive initiator, for example a UVinitiator. The wavelength to react the initiator will depend upon theinitiator properties. Initiators useful for the present inventionpreferably do not react with visible light typically found in a room ora lab as such an initiator would require additional equipment in orderto prevent the reaction from occurring prematurely. Rather, in someembodiments, the initiator can react at a wavelength less than about 280nm and a luminance between about 3 to about 5 mW/cm³. Advantageously,the initiator does not need to be attached to the crosslinker prior toreacting the crosslinker. Rather, when the initiator is used, it cansimply be added to the reaction. Furthermore, the initiator becomesactive without heat. Suitable photo initiators include1-hydroxy-cyclohexyl-phenyl-ketone (for example Ciba® IRGACURE® 184), or13-4-(2-Hydroxyethoxy)-phenyl8-2-hydroxy-2-methyl-1-propane-1-one (forexample Ciba® IRGACURE® 2959),2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, or combinationsthereof.

The crosslinkers or network formers serve at least two purposes relevantto the invention. First, the crosslinkers can be used to bond thecoating to a surface of the substrate. Second, the crosslinker can beused to entrap the hydrating polymer and/or an additive. Combinations ofmore than one crosslinkers can be utilized for a particular application.For example, a first crosslinker can be chosen based on its polarity toprovide good adhesion to a surface of a substrate. A second crosslinkercan be selected to provide lubricity to the coating and to increase thestrength of entanglement of the high molecular weight hydrating polymer.

A high molecular weight polymer can be entrapped in the crosslinkedpolymer. Suitable high molecular weight polymers will have an averagemolecular weight above about 30,000. The average molecular weight of thehigh molecular weight polymers can be between about 30,000 and about1.5M. Low molecular weight polymers would not be suitable for theinvention because they would not entrap within the crosslinked polymer.Suitable high molecular weight polymers include polyethylene oxide,polypropylene oxide, polyvinylpyrrolidone (PVP), polyvinyl alcohol, apolyacrylate, an agarose, a methylcellulose, hyaluronan, polyisocynade,polyethylene oxide, alginate, carboxymethyl cellulose, a urethanecoating, a water miscible epoxide, and the like, and combinations of twoor more of these high molecular weight polymers.

The concentration of each crosslinker components in the coating can bebetween about 0.01 wt. % and 0.5 wt. % of the total mass of the coating.When more than one crosslinker is utilized, then the total concentrationof all crosslinker components is between about 0.02 wt. % and about 2wt. % of the total mass of the coating. In some embodiments where morethan one crosslinker is utilized, the coating can include between 0.01wt. % and about 2 wt. % of a crosslinker or chain extending compound,and between about 0.01 wt. % and about 2.0 wt. % of each additionalcrosslinking or chain extending compound. The ratio of the firstcrosslinker to a second crosslinker can be between about 1:0.1 and about1:1. The concentration of the high molecular weight polymer in thecoating can be between about 3 wt. % and about 15 wt. % of the coating.The concentration of the coating solution in a solvent can be betweenabout 3 wt. % and about 15 wt. %. The solvent can be present in thecoating in an amount between about 85 wt. % and about 97 wt. %.Additives can be present in the coating in an amount between 0.05 wt. %and 0.1 wt. %. Other incidental materials (for example unreactedcomponents) can be present in the coating in an amount less than about0.1 wt. % of the total weight percent of the coating.

The thickness of the coating on the substrate can be between about 0.5microns and about 10 microns. The use of the substrate can dictate thethickness of the coating. A thickness of between about 0.5 microns andabout 10 micron can provide if the coating requires a longer dry-outtime.

In some embodiments of the invention, additives can be incorporated intothe coating. Suitable additives include antimicrobial (includingantibacterial) agents, binders, rheology modifiers, or colorants, andcombinations of two or more additives. Suitable antimicrobial agents caninclude a silver compound, chlorhexidine, ciprofloxacin, andcombinations thereof. Suitable rheology modifiers can include pluronics,alginates, carboxymethyl cellulose and combinations thereof. Suitablecolorants can include dyes or oxide pigments, and combinations thereof.The total concentration of the additives in the coating can be betweenabout 0.05 wt. % and about 0.1 wt. % of the total weight of the coating,with each additive used contributing to a portion of this total weight.

An aspect of the invention is a coating for use on a medical device. Thecoating includes a crosslinked polymer, and at least one polymer. Thecoating provides a polar gradient when applied to a substrate.

The substrate can be contact lenses, catheters (including cardiovascularcatheters and urological catheters), wires (including guidewires),springs, leads (for example a pacemaker lead), stents, implants,antennas, sensors, tubing, syringes, catheters, i.v. bag needles,needles, ventricular assist device components, and trochars, orcombinations of two or more of these devices. The material of thesubstrate can be a polymer, a metal, a glass, polyester block amides(for example Pebax™, a silicone rubber, nylons, polyvinylchlorides,styrene ethylene butadienes (SEBs), and combinations thereof. In someembodiments, the polar characteristic of the exterior surface of thesubstrate can be altered to assist in bonding of the coating, or toalter the alignment of the polarity or hydrophobic/hydrophilic nature ofthe coating at the surface between the coating and the substrate or onthe exterior or outer surface of the coating. By way of example, thepolar characteristic of the exterior surface of a substrate can bealtered from hydrophobic to less hydrophobic as compared to its initialpolar characteristic, or from hydrophilic to less hydrophilic ascompared to its initial polar characteristic. When more than onematerial is used in a medical device, the polar characteristic of thesubstrate can be different at different locations corresponding to thedifferent materials. The medical device can be used in contact withblood, plasma, and the like.

The polar characteristic of the substrate can result in the substratebeing hydrophobic or hydrophilic. The polar characteristic can varythrough the coating, such that the coating is hydrophobic at ansubstrate surface of the coating, gradually increasing in hydrophilicproperties to the exterior surface which is more hydrophilic, or atleast less hydrophobic, compared to the characteristic at the substratesurface of the coating. Alternatively, the polar characteristic can varythrough the coating, such that the coating is hydrophilic at ansubstrate surface of the coating, then gradually decreases inhydrophilic properties, such that the exterior surface is hydrophobic,or at least less hydrophilic, compared to the characteristic at thesubstrate surface of the coating. If more than one crosslinking materialis utilized, the additional crosslinker can also vary in a similarmanner as the first crosslinking material. For example, if a firstcrosslinker is more hydrophilic than a second crosslinker, and asubstrate is hydrophilic, the crosslinking components can align suchthat the first crosslinker is adjacent to the surface of the substrateand second crosslinker in the coating is closer to the outer surface ofthe coating. If additional crosslinkers are used in the coating, thevariation and alignment of the additional crosslinkers can be located inthe coating based on the polarity and hydrophobic/hydrophilic naturecompared to other crosslinking materials in the coating. In someembodiments when more than one crosslinker is utilized, the differentcrosslinkers can not only crosslink with other similar crosslinkers, butcan also crosslink with different crosslinkers, which can result inadditional polarities of the crosslinked material within the overallcrosslinked material.

In some embodiments, for example where only one crosslinker is utilizedin the coating, layering of the coating can be achieved based on thedensity variations in the coatings. In some embodiments, the coating canbe more dense at an substrate surface where the coating bonds orassociates to a surface of the substrate and less dense on the exteriorsurface of the coating. In other embodiments, the coating can be lessdense at an substrate surface compared to the density of the coating atan outer surface.

The polar characteristic of the coating can allow for the coating andthe substrate to create a bond. Thus, an advantage of the presentinvention is that the coating adheres to the substrate. The strength ofthe bond between the substrate and the coating can be between about 1 gmand about 500 gm. In some embodiments, when the entire substrateincludes the coating, then the coating can bond to itself forming asleeve around the substrate. The sleeve embodiment can be useful wherethe substrate is not likely to bond to the coating, but can also provideadditional strength between the coating and the substrate even when thecoating and the substrate create a bond.

The coating can be tailored for particular applications. For example, ifan application requires that the bond between the substrate and thecoating is strong, then the coating can be tailored so that it bondswith the substrate. For example, if the substrate is a polymer and theexterior surface of the polymer substrate is hydrophobic, then thecoating can be formed such that the coating exhibits a gradient wherethe hydrophobic crosslinker is close to the substrate and morehydrophilic crosslinkers are located at the surface. Embodiments of theinvention can result in the middle of the film providing additionalstrength to the coating by mono-functional network formers that haveintermediate concentration of the crosslinker that is designed to adsorbto the surface of the substrate and that of the crosslinker or networkformer selected to reside on the film surface. The vinyl polyethyleneand polypropylene oxides are such compounds which can be used as acrosslinker. Other embodiments can increase the water content of thecoating by addition of hydroxylated compounds as methacrylic acid (MAA),which can be used as a crosslinker. More than one of these embodimentscan be combined to tailor the coating for a particular application.Furthermore, it is possible to produce more than one layer or more thanone coating layers such that there are multiple layers in the coatingcreated by using the same or different coating materials on thesubstrate. In some embodiments, the coating can comprise between aboutone and about five layers, where each layer can be the same ordifferent. The coating can be on a portion of the first surface of thesubstrate such that between about 1% and about 99% of the first surfaceis coated with the coating. The coating can be on a portion of one ormore surfaces of the substrate such that between about 1% and about 99%of at least one surface of the substrate can be coated. In someembodiments, the coating can be on the entire first surface or on morethan one surface of the substrate such that it covers each surface ofthe substrate.

The gradient can be modulated by the choice of solvent used with thecoating, the drying time (evaporation rate), temperature, and itspolarity. By decreasing the polarity with a less polar solvent, a lesspolar crosslinker or network former can disperse into the coating. Amore polar solvent can force a less polar crosslinker to the surface ofthe coating. The solvent can be any suitable alcohol, includingisopropanol, polypropanol, propanol, ethanol, methanol, dimethylsulfoxide (DMSO), water and combinations of. The drying time can bebetween about 2 minutes and about 10 minutes, in some embodimentsbetween about 4 minutes and about 5 minutes. The drying temperature canbe between about 20° C. and about 50° C., in some embodiments betweenabout 27° C. and about 40° C., in some embodiments about 35° C. Thedrying time can depend on the coating thickness and solvent vaporpressure.

At least one crosslinker or network former can be used to create thecrosslinked polymer, or the networked polymer. The crosslinker can be avinyl compound (including polyvinyl ethylene glycol, polyvinyl siloxane,vinyl pyrrolidone, vinyl silanes, vinyl polyethylene oxide, and vinylpolypropylene oxide), ethyleneglycol dimethacrylate, an acrylatecompound (for example MAA), an epoxy compound, a urethane compound, anisocyanate compounds, triacrylate (for example, trimethylolpropanetriacrylate), methacrylate, methacrylic acid, and hydroxyethylmethacrylate, and combinations or two or more of these crosslinkers. Thecrosslinker can be activated by free radical or ionic mechanisms or bydehydration to produce the crosslinked polymer with an initiator. Theinitiator can be a photo or radioactive initiator, for example a UVinitiator. The wavelength to react the initiator will depend upon theinitiator properties. Initiators useful for the present inventionpreferably do not react with visible light typically found in a room ora lab as such an initiator would require additional equipment in orderto prevent the reaction from occurring prematurely. Rather, in someembodiments, the initiator can react at a wavelength less than about 280nm and a luminance between about 3 to about 5 mW/cm³. Advantageously,the initiator does not need to be attached to the crosslinker prior toreacting the crosslinker. Rather, when the initiator is used, it cansimply be added to the reaction. Furthermore, the initiator becomesactive without heat. Suitable photo initiators include1-hydroxy-cyclohexyl-phenyl-ketone (for example Ciba® IRGACURE® 184), or13-4-(2-Hydroxyethoxy)-phenyl8-2-hydroxy-2-methyl-1-propane-1-one (forexample Ciba® IRGACURE® 2959),2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, or combinationsthereof.

The crosslinkers or network formers serve at least two purposes relevantto the invention. First, the crosslinkers can be used to bond thecoating to a surface of the substrate. Second, the crosslinker can beused to entrap the hydrating polymer and/or an additive. Combinations ofmore than one crosslinkers can be utilized for a particular application.For example, a first crosslinker can be chosen based on its polarity toprovide good adhesion to a surface of a substrate. A second crosslinkercan be selected to provide lubricity to the coating and to increase thestrength of entanglement of the high molecular weight hydrating polymer.

A high molecular weight polymer can be entrapped in the crosslinkedpolymer. Suitable high molecular weight polymers will have an averagemolecular weight above about 30,000. The average molecular weight of thehigh molecular weight polymers can be between about 30,000 and about1.5M. Low molecular weight polymers would not be suitable for theinvention because they would not entrap within the crosslinked polymer.Suitable high molecular weight polymers include polyethylene oxide,polypropylene oxide, polyvinylpyrrolidone (PVP), polyvinyl alcohol, apolyacrylate, an agarose, a methylcellulose, hyaluronan, polyisocynade,polyethylene oxide, alginate, carboxymethyl cellulose, a urethanecoating, a water miscible epoxide, and the like, and combinations of twoor more of these high molecular weight polymers.

The concentration of each crosslinker components in the coating can bebetween about 0.01 wt. % and 0.5 wt. % of the total mass of the coating.When more than one crosslinker is utilized, then the total concentrationof all crosslinker components is between about 0.02 wt. % and about 2wt. % of the total mass of the coating. In some embodiments where morethan one crosslinker is utilized, the coating can include between 0.01wt. % and about 2 wt. % of a crosslinker or chain extending compound,and between about 0.01 wt. % and about 2.0 wt. % of each additionalcrosslinking or chain extending compound. The ratio of the firstcrosslinker to a second crosslinker can be between about 1:0.1 and about1:1. The concentration of the high molecular weight polymer in thecoating can be between about 3 wt. % and about 15 wt. % of the coating.The concentration of the coating solution in a solvent can be betweenabout 3 wt. % and about 15 wt. %. The solvent can be present in thecoating in an amount between about 85 wt. % and about 97 wt. %.Additives can be present in the coating in an amount between 0.05 wt. %and 0.1 wt. %. Other incidental materials (for example unreactedcomponents) can be present in the coating in an amount less than about0.1 wt. % of the total weight percent of the coating.

The thickness of the coating on the substrate can be between about 0.5microns and about 10 microns. The use of the substrate can dictate thethickness of the coating. A thickness of between about 0.5 microns andabout 10 micron can provide if the coating requires a longer dry-outtime.

In some embodiments of the invention, additives can be incorporated intothe coating. Suitable additives include antimicrobial (includingantibacterial) agents, binders, rheology modifiers, or colorants, andcombinations of two or more additives. Suitable antimicrobial agents caninclude a silver compound, chlorhexidine, ciprofloxacin, andcombinations thereof. Suitable rheology modifiers can include pluronics,alginates, carboxymethyl cellulose and combinations thereof. Suitablecolorants can include dyes or oxide pigments, and combinations thereof.The total concentration of the additives in the coating can be betweenabout 0.05 wt. % and about 0.1 wt. % of the total weight of the coating,with each additive used contributing to a portion of this total weight.

An aspect of the invention is a gradient coating. The coating includes acrosslinked polymer and a high molecular weight polymer, wherein thegradient in the gradient coating is based on density of the crosslinkerof the crosslinked polymer.

The substrate can be contact lenses, catheters (including cardiovascularcatheters and urological catheters), wires (including guidewires),springs, leads (for example a pacemaker lead), stents, implants,antennas, sensors, tubing, syringes, catheters, i.v. bag needles,needles, ventricular assist device components, and trochars, orcombinations of two or more of these devices. The material of thesubstrate can be a polymer, a metal, a glass, polyester block amides(for example Pebax™, a silicone rubber, nylons, polyvinylchlorides,styrene ethylene butadienes (SEBs), and combinations thereof. In someembodiments, the polar characteristic of the exterior surface of thesubstrate can be altered to assist in bonding of the coating, or toalter the alignment of the polarity or hydrophobic/hydrophilic nature ofthe coating at the surface between the coating and the substrate or onthe exterior or outer surface of the coating. By way of example, thepolar characteristic of the exterior surface of a substrate can bealtered from hydrophobic to less hydrophobic as compared to its initialpolar characteristic, or from hydrophilic to less hydrophilic ascompared to its initial polar characteristic. When more than onematerial is used in a medical device, the polar characteristic of thesubstrate can be different at different locations corresponding to thedifferent materials. The medical device can be used in contact withblood, plasma, and the like.

The polar characteristic of the substrate can result in the substratebeing hydrophobic or hydrophilic. The polar characteristic can varythrough the coating, such that the coating is hydrophobic at ansubstrate surface of the coating, gradually increasing in hydrophilicproperties to the exterior surface which is more hydrophilic, or atleast less hydrophobic, compared to the characteristic at the substratesurface of the coating. Alternatively, the polar characteristic can varythrough the coating, such that the coating is hydrophilic at ansubstrate surface of the coating, then gradually decreases inhydrophilic properties, such that the exterior surface is hydrophobic,or at least less hydrophilic, compared to the characteristic at thesubstrate surface of the coating. If more than one crosslinking materialis utilized, the additional crosslinker can also vary in a similarmanner as the first crosslinking material. For example, if a firstcrosslinker is more hydrophilic than a second crosslinker, and asubstrate is hydrophilic, the crosslinking components can align suchthat the first crosslinker is adjacent to the surface of the substrateand second crosslinker in the coating is closer to the outer surface ofthe coating. If additional crosslinkers are used in the coating, thevariation and alignment of the additional crosslinkers can be located inthe coating based on the polarity and hydrophobic/hydrophilic naturecompared to other crosslinking materials in the coating. In someembodiments when more than one crosslinker is utilized, the differentcrosslinkers can not only crosslink with other similar crosslinkers, butcan also crosslink with different crosslinkers, which can result inadditional polarities of the crosslinked material within the overallcrosslinked material.

In some embodiments, for example where only one crosslinker is utilizedin the coating, layering of the coating can be achieved based on thedensity variations in the coatings. In some embodiments, the coating canbe more dense at an substrate surface where the coating bonds orassociates to a surface of the substrate and less dense on the exteriorsurface of the coating. In other embodiments, the coating can be lessdense at an substrate surface compared to the density of the coating atan outer surface.

The polar characteristic of the coating can allow for the coating andthe substrate to create a bond. Thus, an advantage of the presentinvention is that the coating adheres to the substrate. The strength ofthe bond between the substrate and the coating can be between about 1 gmand about 500 gm. In some embodiments, when the entire substrateincludes the coating, then the coating can bond to itself forming asleeve around the substrate. The sleeve embodiment can be useful wherethe substrate is not likely to bond to the coating, but can also provideadditional strength between the coating and the substrate even when thecoating and the substrate create a bond.

The coating can be tailored for particular applications. For example, ifan application requires that the bond between the substrate and thecoating is strong, then the coating can be tailored so that it bondswith the substrate. For example, if the substrate is a polymer and theexterior surface of the polymer substrate is hydrophobic, then thecoating can be formed such that the coating exhibits a gradient wherethe hydrophobic crosslinker is close to the substrate and morehydrophilic crosslinkers are located at the surface. Embodiments of theinvention can result in the middle of the film providing additionalstrength to the coating by mono-functional network formers that haveintermediate concentration of the crosslinker that is designed to adsorbto the surface of the substrate and that of the crosslinker or networkformer selected to reside on the film surface. The vinyl polyethyleneand polypropylene oxides are such compounds which can be used as acrosslinker. Other embodiments can increase the water content of thecoating by addition of hydroxylated compounds as methacrylic acid (MAA),which can be used as a crosslinker. More than one of these embodimentscan be combined to tailor the coating for a particular application.Furthermore, it is possible to produce more than one layer or more thanone coating layers such that there are multiple layers in the coatingcreated by using the same or different coating materials on thesubstrate. In some embodiments, the coating can comprise between aboutone and about five layers, where each layer can be the same ordifferent. The coating can be on a portion of the first surface of thesubstrate such that between about 1% and about 99% of the first surfaceis coated with the coating. The coating can be on a portion of one ormore surfaces of the substrate such that between about 1% and about 99%of at least one surface of the substrate can be coated. In someembodiments, the coating can be on the entire first surface or on morethan one surface of the substrate such that it covers each surface ofthe substrate.

The gradient can be modulated by the choice of solvent used with thecoating, the drying time (evaporation rate), temperature, and itspolarity. By decreasing the polarity with a less polar solvent, a lesspolar crosslinker or network former can disperse into the coating. Amore polar solvent can force a less polar crosslinker to the surface ofthe coating. The solvent can be any suitable alcohol, includingisopropanol, polypropanol, propanol, ethanol, methanol, dimethylsulfoxide (DMSO), water and combinations of. The drying time can bebetween about 2 minutes and about 10 minutes, in some embodimentsbetween about 4 minutes and about 5 minutes. The drying temperature canbe between about 20° C. and about 50° C., in some embodiments betweenabout 27° C. and about 40° C., in some embodiments about 35° C. Thedrying time can depend on the coating thickness and solvent vaporpressure.

At least one crosslinker or network former can be used to create thecrosslinked polymer, or the networked polymer. The crosslinker can be avinyl compound (including polyvinyl ethylene glycol, polyvinyl siloxane,vinyl pyrrolidone, vinyl silanes, vinyl polyethylene oxide, and vinylpolypropylene oxide), ethyleneglycol dimethacrylate, an acrylatecompound (for example MAA), an epoxy compound, a urethane compound, anisocyanate compounds, triacrylate (for example, trimethylolpropanetriacrylate), methacrylate, methacrylic acid, and hydroxyethylmethacrylate, and combinations or two or more of these crosslinkers. Thecrosslinker can be activated by free radical or ionic mechanisms or bydehydration to produce the crosslinked polymer with an initiator. Theinitiator can be a photo or radioactive initiator, for example a UVinitiator. The wavelength to react the initiator will depend upon theinitiator properties. Initiators useful for the present inventionpreferably do not react with visible light typically found in a room ora lab as such an initiator would require additional equipment in orderto prevent the reaction from occurring prematurely. Rather, in someembodiments, the initiator can react at a wavelength less than about 280nm and a luminance between about 3 to about 5 mW/cm³. Advantageously,the initiator does not need to be attached to the crosslinker prior toreacting the crosslinker. Rather, when the initiator is used, it cansimply be added to the reaction. Furthermore, the initiator becomesactive without heat. Suitable photo initiators include1-hydroxy-cyclohexyl-phenyl-ketone (for example Ciba® IRGACURE® 184), or13-4-(2-Hydroxyethoxy)-phenyl8-2-hydroxy-2-methyl-1-propane-1-one (forexample Ciba® IRGACURE® 2959),2-Hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone, or combinationsthereof.

The crosslinkers or network formers serve at least two purposes relevantto the invention. First, the crosslinkers can be used to bond thecoating to a surface of the substrate. Second, the crosslinker can beused to entrap the hydrating polymer and/or an additive. Combinations ofmore than one crosslinkers can be utilized for a particular application.For example, a first crosslinker can be chosen based on its polarity toprovide good adhesion to a surface of a substrate. A second crosslinkercan be selected to provide lubricity to the coating and to increase thestrength of entanglement of the high molecular weight hydrating polymer.

A high molecular weight polymer can be entrapped in the crosslinkedpolymer. Suitable high molecular weight polymers will have an averagemolecular weight above about 30,000. The average molecular weight of thehigh molecular weight polymers can be between about 30,000 and about1.5M. Low molecular weight polymers would not be suitable for theinvention because they would not entrap within the crosslinked polymer.Suitable high molecular weight polymers include polyethylene oxide,polypropylene oxide, polyvinylpyrrolidone (PVP), polyvinyl alcohol, apolyacrylate, an agarose, a methylcellulose, hyaluronan, polyisocynade,polyethylene oxide, alginate, carboxymethyl cellulose, a urethanecoating, a water miscible epoxide, and the like, and combinations of twoor more of these high molecular weight polymers.

The concentration of each crosslinker components in the coating can bebetween about 0.01 wt. % and 0.5 wt. % of the total mass of the coating.When more than one crosslinker is utilized, then the total concentrationof all crosslinker components is between about 0.02 wt. % and about 2wt. % of the total mass of the coating. In some embodiments where morethan one crosslinker is utilized, the coating can include between 0.01wt. % and about 2 wt. % of a crosslinker or chain extending compound,and between about 0.01 wt. % and about 2.0 wt. % of each additionalcrosslinking or chain extending compound. The ratio of the firstcrosslinker to a second crosslinker can be between about 1:0.1 and about1:1. The concentration of the high molecular weight polymer in thecoating can be between about 3 wt. % and about 15 wt. % of the coating.The concentration of the coating solution in a solvent can be betweenabout 3 wt. % and about 15 wt. %. The solvent can be present in thecoating in an amount between about 85 wt. % and about 97 wt. %.Additives can be present in the coating in an amount between 0.05 wt. %and 0.1 wt. %. Other incidental materials (for example unreactedcomponents) can be present in the coating in an amount less than about0.1 wt. % of the total weight percent of the coating.

The thickness of the coating on the substrate can be between about 0.5microns and about 10 microns. The use of the substrate can dictate thethickness of the coating. A thickness of between about 0.5 microns andabout 10 micron can provide if the coating requires a longer dry-outtime.

In some embodiments of the invention, additives can be incorporated intothe coating. Suitable additives include antimicrobial (includingantibacterial) agents, binders, rheology modifiers, or colorants, andcombinations of two or more additives. Suitable antimicrobial agents caninclude a silver compound, chlorhexidine, ciprofloxacin, andcombinations thereof. Suitable rheology modifiers can include pluronics,alginates, carboxymethyl cellulose and combinations thereof. Suitablecolorants can include dyes or oxide pigments, and combinations thereof.The total concentration of the additives in the coating can be betweenabout 0.05 wt. % and about 0.1 wt. % of the total weight of the coating,with each additive used contributing to a portion of this total weight.

EXAMPLES Example 1

This example illustrates the preparation of two coating compositions inaccordance with the present invention.

Coating compositions A and B were prepared by combining the ingredientsin the relative amounts by mass shown in Table 1.

TABLE 1 Composi- Composi- Composi- Component tion A tion B tion CPolyvinylpyrrolidone (PVP) 1.0 3.0  1.0  Trimethylolpropane  0.15 0.0250.15 triacrylate (TMPTA) Methacrylic acid (MAA) — 0.15  0.05Ethyleneglycol — 0.025 — dimethacrylate (EGDMA) Irgacure 184   0.0075 —0.1  Irgacure 2959 — 0.01  —

Isopropyl alcohol was added as a solvent in an amount of 5 weightpercent of the composition.

Example 2

This example illustrates the production of a catheter coated withComposition A. A urological catheter made of polyethylene was coatedwith Composition A and then subjected to UV radiation with a wavelengthbelow 280 nm and luminance of 3 to 5 mW/cm² to initiate crosslinking.The resulting coated catheter has a coating that is well bonded to thecatheter and has a high water content and a long dry out time.

Example 3

This example illustrates the production of a catheter coated withComposition B. A urological catheter made of polyethylene was coatedwith Composition B and then subjected to UV radiation with a wavelengthbelow 280 nm and luminance of 3 to 5 mW/cm² to initiate crosslinking.The resulting coated catheter has a coating that is well bonded to thecatheter and has a high water content and a long dry out time.

Example 4

This example illustrates the production of a catheter coated withComposition C. The total concentration of the coating solution rangesbetween about 3% and about 7%. A urological catheter made ofpolyvinylchloride was coated with Composition A and then subjected to UVradiation with a wavelength below 280 nm and luminance of 3 to 5 mW/cm²to initiate crosslinking. The resulting coated catheter has a coatingthat is well bonded to the catheter and has a high water content and along dry out time.

Example 5

This example illustrates the average frictional force of the coating forfifty cycles (unless noted) for different compositions. Table 2 providesthe average frictional force for these compositions. The nomenclature ofthe different compositions is as follows: First number corresponds witha solvent—5 is IPA, and 6 is methanol; the second number correspondswith the composition of the coating—1 is Composition A, 2 is CompositionB; the third number indicates whether a low amount of a crosslinker wasused which is indicated by the number 0, while a high amount of thecrosslinker is indicated with 6; the letter indicates a test sample.This data therefore accounts for different solvents used in thecoatings, and whether there is a low total amount of a crosslinker(about 0.05 wt. %) or combination of crosslinkers compared to a higheramount of a crosslinker (about 2 weight %) in the coating.

TABLE 2 Average Frictional Sample Force (gm) 510a 9.17 510b 10.48 510c8.95 (15 cycles) 510d 29.4 526e 20.19 526e 15.08 526f 29.71 616a 14.89616b 21.66 626c 17.06 626d 20.27 626e 9.83 626f 20.01

Ranges have been discussed and used within the forgoing description. Oneskilled in the art would understand that any sub-range within the statedrange would be suitable, as would any number within the broad range,without deviating from the invention.

The foregoing description of the present invention has been presentedfor purposes of illustration and description. Furthermore, thedescription is not intended to limit the invention to the form disclosedherein. Consequently, variations and modifications commensurate with theabove teachings, and the skill or knowledge of the relevant art, arewithin the scope of the present invention. The embodiment describedhereinabove is further intended to explain the best mode known forpracticing the invention and to enable others skilled in the art toutilize the invention in such, or other, embodiments and with variousmodifications required by the particular applications or uses of thepresent invention. It is intended that the appended claims be construedto include alternative embodiments to the extent permitted by the priorart.

The invention claimed is:
 1. A polymerizable coating composition,comprising: an initiator; a crosslinker configured to form a crosslinkedpolymer; a high molecular weight component, wherein the high molecularweight component has an average molecular weight between about 30,000and 1.5M; and a solvent; wherein polymerization of the composition on asubstrate yields a coating comprising the high molecular weightcomponent entrapped in the crosslinked polymer; wherein thepolymerizable coating composition is configured to bond to thesubstrate, thereby forming a coating on the substrate, wherein theformed coating comprises a polar characteristic, and wherein the polarcharacteristic varies through the coating, such that the coating ishydrophobic at a substrate surface of the coating, gradually increasingin hydrophilic properties to an exterior surface of the coating which ismore hydrophilic compared to the substrate surface of the coating. 2.The coating composition of claim 1, wherein the crosslinker comprisesabout 0.01 wt % to about 0.5 wt % of the polymerizable coatingcomposition.
 3. The coating composition of claim 1, wherein the highmolecular weight component comprises about 3 wt % to about 15 wt % ofthe polymerizable coating composition.
 4. The coating composition ofclaim 1, wherein the solvent comprises about 85 wt % to about 97 wt % ofthe polymerizable coating composition.
 5. The coating composition ofclaim 1, wherein a ratio of the crosslinker, the high molecular weightcomponent, and the initiator is between about 1:0.1:0.005 and about0.02:1.0:0.02.
 6. The coating composition of claim 5, wherein the ratiois about 1:0.15:0.0075.
 7. The coating composition of claim 1, whereinthe initiator is a photo reactive initiator.
 8. The coating compositionof claim 1, wherein the initiator reacts at a wavelength less than about280 nm and a minimal luminance between about 3 to about 5 mW/cm².
 9. Thecoating composition of claim 1, further comprising an additionalcrosslinker.
 10. The coating composition of claim 9, wherein thecrosslinker and the additional crosslinker stratify in the coating suchthat the first crosslinker arranges in a first layer and the secondcrosslinker arranges in a second layer.
 11. The coating composition ofclaim 1, wherein the crosslinker comprises a polyvinyl ethylene glycol,a polyvinyl siloxane, a vinyl pyrrolidone, a vinyl silane, a vinylpolyethylene oxide, a vinyl polypropylene oxide, or any combinationthereof.
 12. The coating composition of claim 1, further comprising anadditional crosslinker, wherein the additional crosslinker is differentfrom the crosslinker.
 13. The coating composition of claim 12, whereinthe additional crosslinker comprises a vinyl compound, an ethyleneglycoldimethacrylate, an acrylate compound, an epoxy compound, a urethanecompound, an isocyanate compounds, a triacrylate, a methacrylate, amethacrylic acid, or a hydroxyethyl methacrylate.
 14. The coatingcomposition of claim 1, further comprising an additional crosslinker,wherein a ratio of the crosslinker to the additional crosslinker isbetween about 1:0.1 and about 1:10.
 15. The coating composition of claim14, wherein the ratio of the crosslinker to the additional crosslinkeris between about 1:0.1 and about 1:1.
 16. The coating composition ofclaim 1, further comprising an additive, wherein the additive is exposedat an outer surface of the coating or an exterior surface of thesubstrate.
 17. The coating composition of claim 1, wherein the solventcomprises isopropanol, polypropanol, propanol, ethanol, methanol,dimethyl sulfoxide, water, or any combination thereof.
 18. The coatingcomposition of claim 1, wherein the high molecular weight componentcomprises polyethylene oxide, polypropylene oxide, polyvinylpyrrolidone(PVP), polyvinyl alcohol, a polyacrylate, an agarose, a methylcellulose,hyaluronan, polyisocynade, polyethylene oxide, alginate, carboxymethylcellulose, a urethane coating, a water miscible epoxide, or anycombination thereof.
 19. The coating composition of claim 1, wherein thecrosslinker induces a variable concentration of at least one hydrophiliccomponent of the coating composition between the coating adjacent to anexterior surface of the substrate and an outer surface of the coatingresulting in a variable hydrophilic nature of the coating providinggreater water absorption near the outer surface of the coating relativeto the coating adjacent to an exterior surface of the substrate.
 20. Apolymerizable coating composition, comprising: an initiator; acrosslinker configured to form a crosslinked polymer; a high molecularweight component, wherein the high molecular weight component has anaverage molecular weight between about 30,000 and 1.5M; and a solvent;wherein polymerization of the composition on a substrate yields acoating comprising the high molecular weight component entrapped in thecrosslinked polymer; wherein the polymerizable coating composition isconfigured to covalently bond to the substrate, thereby forming acoating on the substrate.